Variant Annotation
Available parameters and response documentation is available here
GET /lookup/KRAS:G12D?add-AMP-annotation=1
{ "chromosome": "chr12", "alt": "T", "ref": "C", "pos": 25398284, "variant_id": "10190120253982840004", "regions": { "uniprot_regions": { "version": "07-Feb-2025", "items": [ { "absolute_positon": 545190166, "amino_acid": "M1-E37,D38-R97,R97-Q150,R151-M189", "chromo": "chr12", "colour": "255,0,0", "description": null, "length": 45684, "position": 25358180, "protein": "RASK_HUMAN", "type": "homo_sapiens proteome sequences", "pub_med_references": null }, { "absolute_positon": 545230251, "amino_acid": "G10-A18", "chromo": "chr12", "colour": "0,102,153", "description": "Other binding site_10-18", "length": 27, "position": 25398265, "protein": "RASK_HUMAN", "type": "binding site", "pub_med_references": null } ] }, "nih_gtex": { "version": "v10", "items": [ { "GTExJsonData": { "exon_id": "ENSG00000133703.14_3", "exon_number": "3", "expressions": { "adipose_subcutaneous": 0.24780000000000002, "adipose_visceral_omentum": 0.23040000000000002, "adrenal_gland": 0.14640000000000003, "artery_aorta": 0.16600000000000004, "artery_coronary": 0.18430000000000002, "artery_tibial": 0.2547, "bladder": 0.28900000000000003, "brain_amygdala": 0.07314000000000001, "brain_anterior_cingulate_cortex_ba24": 0.12270000000000002, "brain_caudate_basal_ganglia": 0.08968000000000002, "brain_cerebellar_hemisphere": 0.22770000000000004, "brain_cerebellum": 0.11920000000000003, "brain_cortex": 0.10820000000000002, "brain_frontal_cortex_ba9": 0.15000000000000002, "brain_hippocampus": 0.07127000000000001, "brain_hypothalamus": 0.12060000000000001, "brain_nucleus_accumbens_basal_ganglia": 0.09925000000000003, "brain_putamen_basal_ganglia": 0.05843000000000001, "brain_spinal_cord_cervical_c_1": 0.08599000000000002, "brain_substantia_nigra": 0.08305000000000001, "breast_mammary_tissue": 0.20350000000000001, "cells_cultured_fibroblasts": 0.4822, "cells_ebv_transformed_lymphocytes": 0.7015, "cervix_ectocervix": 0.20870000000000002, "cervix_endocervix": 0.1345, "colon_sigmoid": 0.19640000000000005, "colon_transverse": 0.2731, "esophagus_gastroesophageal_junction": 0.2338, "esophagus_mucosa": 0.4312, "esophagus_muscularis": 0.2765, "fallopian_tube": 0.16740000000000005, "heart_atrial_appendage": 0.11540000000000002, "heart_left_ventricle": 0.07880000000000001, "kidney_cortex": 0.11110000000000002, "kidney_medulla": 0.13740000000000002, "liver": 0.0748, "lung": 0.2681, "minor_salivary_gland": 0.2847, "muscle_skeletal": 0.1267, "nerve_tibial": 0.2916, "ovary": 0.11820000000000003, "pancreas": 0.1048, "pituitary": 0.08331000000000001, "prostate": 0.12090000000000001, "skin_not_sun_exposed_suprapubic": 0.21860000000000002, "skin_sun_exposed_lower_leg": 0.2436, "small_intestine_terminal_ileum": 0.24810000000000001, "spleen": 0.12360000000000002, "stomach": 0.21800000000000003, "testis": 0.23240000000000002, "thyroid": 0.16120000000000004, "uterus": 0.15950000000000003, "vagina": 0.2431, "whole_blood": 0.2826 }, "gencode_id": "ENSG00000133703", "gene": "\"KRAS\"", "gene_model_positions": { "chromosome": "chr12", "end": 25403870, "start": 25358180, "strand": "-" }, "gene_positions": { "chromosome": "chr12", "end": 25403870, "start": 25358180, "strand": "-" } }, "absolute_positon": 545230195, "chromo": "chr12", "length": 121, "position": 25398209 } ] } }, "variant_type": "SNV", "cytobands": "12p12.1", "refseq_transcripts": [ { "items": [ { "name": "NM_004985.5", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 5 position 46 of 122", "coding_location": "12 of 189", "canonical": true, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": "ENST00000311936.8", "mane_plus": null, "uniprot_id": null }, { "name": "NM_033360.4", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 6 position 46 of 122", "coding_location": "12 of 190", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": null, "mane_plus": "ENST00000256078.10", "uniprot_id": null }, { "name": "NM_001369786.1", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 6 position 46 of 122", "coding_location": "12 of 190", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null }, { "name": "NM_001369787.1", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 5 position 46 of 122", "coding_location": "12 of 189", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null } ], "version": "228" } ], "ensembl_transcripts": [ { "items": [ { "name": "ENST00000256078.4", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 6 position 46 of 122", "coding_location": "12 of 190", "canonical": true, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": "1", "ensembl_appris": "alternative1", "mane_select": null, "mane_plus": "NM_033360.4", "uniprot_id": "P01116" }, { "name": "ENST00000311936.3", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 5 position 46 of 122", "coding_location": "12 of 189", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": "1", "ensembl_appris": "principal4", "mane_select": "NM_004985.5", "mane_plus": null, "uniprot_id": "P01116" }, { "name": "ENST00000556131.1", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 3 position 46 of 122", "coding_location": "12 of 44", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": "1", "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null }, { "name": "ENST00000557334.1", "strand": "-", "coding_impact": "missense", "function": [ "coding" ], "hgvs": "c.35G>A", "hgvs_p1": "G12D", "hgvs_p3": "p.(Gly12Asp)", "location": "exon 2 of 3 position 46 of 122", "coding_location": "12 of 76", "canonical": false, "gene_symbol": "KRAS", "splice_distance": "46", "ensembl_support_level": "5", "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null } ], "version": "113" } ], "gnomad_exomes": [ { "version": "2.1.1", "filter": "PASS", "ac": 1, "an": 249328, "af": 4.010780979272284e-6, "ac_nfe": 1, "ac_nfe_nwe": 1, "ac_nfe_female": 1, "ac_female": 1, "an_afr": 16052, "an_amr": 34444, "an_asj": 9964, "an_eas": 18350, "an_eas_kor": 3816, "an_eas_jpn": 152, "an_eas_oea": 14382, "an_fin": 21608, "an_nfe": 112572, "an_nfe_bgr": 2664, "an_nfe_est": 242, "an_nfe_nwe": 42080, "an_nfe_onf": 30698, "an_nfe_seu": 11380, "an_nfe_swe": 25508, "an_oth": 6098, "an_sas": 30240, "an_afr_male": 6096, "an_amr_male": 14270, "an_asj_male": 5130, "an_eas_male": 9042, "an_fin_male": 11256, "an_nfe_male": 62984, "an_oth_male": 3190, "an_sas_male": 22754, "an_afr_female": 9956, "an_amr_female": 20174, "an_asj_female": 4834, "an_eas_female": 9308, "an_fin_female": 10352, "an_nfe_female": 49588, "an_oth_female": 2908, "an_sas_female": 7486, "an_male": 134722, "an_female": 114606, "age_hist_het_65_70": 1, "variant_type": "multi-snv", "main_data": "ƒ = 0.00000401" } ], "gnomad_exomes_coverage": [ { "version": "2.1", "coverage_mean": [ 59.50400161743164 ], "coverage_median": [ 61.0 ], "coverage_20_frequency": [ 0.8506424146244698 ] } ], "gnomad_genomes_coverage": [ { "version": "2.1", "coverage_mean": [ 31.334999084472656 ], "coverage_median": [ 31.0 ], "coverage_20_frequency": [ 0.9536118655964843 ] } ], "dbnsfp": [ { "version": "4.9", "ensembl_proteinid": [ "ENSP00000308495", "ENSP00000452512", "ENSP00000256078", "ENSP00000451856" ], "ensembl_transcriptid": [ "ENST00000311936", "ENST00000557334", "ENST00000256078", "ENST00000556131" ], "mutationtaster_pred": [ "D", "D", "D", "D" ], "mutationtaster_score": [ 1.0, 1.0, 1.0, 1.0 ], "sift_score": [ 0.01, 0.018, 0.01, 0.024 ], "sift_pred": [ "D", "D", "D", "D" ], "phylop100way_vertebrate": [ 7.892000198364258 ], "phylop46way_placental": null, "phylop46way_primate": null, "mutationtaster_converted_rankscore": [ 0.8100100159645081 ], "mutationassessor_pred": [ "M", null, "M", null ], "mutationassessor_score": [ 2.685, null, 2.685, null ], "mutationassessor_rankscore": [ 0.7855299711227417 ], "fathmm_mkl_coding_pred": [ "D" ], "fathmm_mkl_coding_score": [ 0.9787499904632568 ], "fathmm_mkl_coding_rankscore": [ 0.7778699994087219 ], "fathmm_pred": [ "T", "T", "T", "T" ], "fathmm_score": [ -1.19, -1.19, -1.19, -1.19 ], "fathmm_converted_rankscore": [ 0.7842699885368347 ], "sift_converted_rankscore": [ 0.5645599961280823 ], "metasvm_pred": [ "D" ], "metasvm_score": [ 0.2669999897480011 ], "metasvm_rankscore": [ 0.8702300190925598 ], "metalr_pred": [ "D" ], "metalr_score": [ 0.5809000134468079 ], "metalr_rankscore": [ 0.8492400050163269 ], "provean_pred": [ "D", "D", "D", "D" ], "provean_score": [ -5.27, -6.32, -5.37, -6.33 ], "provean_converted_rankscore": [ 0.9089499711990356 ], "lrt_pred": [ "D" ], "lrt_score": [ 0.0 ], "lrt_converted_rankscore": [ 0.8432999849319458 ], "lrt_omega": [ 0.0 ], "cadd_raw": null, "cadd_raw_rankscore": null, "cadd_phred": null, "gm12878_confidence_value": [ 0.0 ], "gm12878_fitcons_score": [ 0.7096629738807678 ], "gm12878_fitcons_rankscore": [ 0.8118799924850464 ], "siphy_29way_logodds_rankscore": [ 0.9035300016403198 ], "siphy_29way_pi": [ 0.0, 1.0, 0.0, 0.0 ], "siphy_29way_logodds": 18.37190055847168, "phylop20way_mammalian": null, "phylop20way_mammalian_rankscore": null, "phylop100way_vertebrate_rankscore": [ 0.8585799932479858 ], "phastcons20way_mammalian": null, "phastcons20way_mammalian_rankscore": null, "phastcons100way_vertebrate": [ 1.0 ], "phastcons100way_vertebrate_rankscore": [ 0.7163800001144409 ], "vest3_score": null, "vest3_rankscore": null, "aloft_confidence": null, "aloft_fraction_transcripts_affected": null, "aloft_pred": null, "aloft_prob_dominant": null, "aloft_prob_recessive": null, "aloft_prob_tolerant": null, "bstatistic": 707.0, "bstatistic_rankscore": null, "deogen2_pred": [ null, null, "D", null ], "deogen2_rankscore": 0.9623500108718872, "deogen2_score": [ null, null, 0.839213, null ], "eigen_pc_phred_coding": 7.073244094848633, "eigen_pc_raw_coding": 0.6604964733123779, "eigen_pc_raw_coding_rankscore": 0.7939599752426147, "eigen_pred_coding": null, "eigen_raw_coding": 0.6056387424468994, "eigen_raw_coding_rankscore": 0.7353000044822693, "fathmm_xf_coding_score": 0.8918150067329407, "fathmm_xf_coding_rankscore": 0.8281400203704834, "fathmm_xf_coding_pred": [ "D" ], "integrated_confidence_value": 0, "integrated_fitcons_score": 0.7323979735374451, "integrated_fitcons_rankscore": 0.9242200255393982, "h1_hesc_confidence_value": 0, "h1_hesc_fitcons_score": 0.7436710000038147, "h1_hesc_fitcons_rankscore": 0.9607599973678589, "huvec_confidence_value": 0, "huvec_fitcons_score": 0.6316310167312622, "huvec_fitcons_rankscore": 0.49549999833106995, "phylop17way_primate": 0.5799999833106995, "phylop17way_primate_rankscore": 0.29708001017570496, "phylop30way_mammalian": null, "phylop30way_mammalian_rankscore": null, "phastcons17way_primate": 1.0, "phastcons17way_primate_rankscore": 0.9721199870109558, "phastcons30way_mammalian": null, "phastcons30way_mammalian_rankscore": null, "polyphen2_hdiv_pred": null, "polyphen2_hdiv_rankscore": null, "polyphen2_hdiv_score": null, "polyphen2_hvar_pred": null, "polyphen2_hvar_rankscore": null, "polyphen2_hvar_score": null, "primateai_pred": [ "D" ], "primateai_score": [ 0.9290492534637451 ], "primateai_rankscore": [ 0.989329993724823 ], "mpc_score": [ null, null, 2.25690945348, null ], "mpc_rankscore": 0.9614599943161011, "mutpred_score": [ 0.772, 0.772, 0.772, 0.772, null ], "mutpred_rankscore": 0.8984599709510803, "mvp_score": [ 0.957447700615, 0.957447700615, 0.957447700615, 0.957447700615 ], "mvp_rankscore": 0.9569900035858154, "sift4g_score": [ 0.0, 0.0, 0.0, 0.0 ], "sift4g_converted_rankscore": 0.9282400012016296, "sift4g_pred": [ "D", "D", "D", "D" ], "revel_score": [ 0.875, 0.875, 0.875, 0.875 ], "revel_rankscore": 0.9628000259399414, "list_s2_pred": [ "T", "T", "T", "T" ], "list_s2_score": [ 0.557244, 0.333767, 0.331367, 0.333767 ], "list_s2_rankscore": 0.19380000233650208, "bayesdel_addaf_pred": [ "D" ], "bayesdel_addaf_score": 0.39786601066589355, "bayesdel_addaf_rankscore": 0.8979099988937378, "bayesdel_noaf_pred": [ "D" ], "bayesdel_noaf_score": 0.333730012178421, "bayesdel_noaf_rankscore": 0.8966299891471863, "metarnn_pred": [ "D", "D", "D", "D" ], "metarnn_score": [ 0.897719, 0.897719, 0.897719, 0.897719 ], "metarnn_rankscore": 0.8912799954414368, "m_cap_pred": [ "D" ], "m_cap_score": 0.1646459996700287, "m_cap_rankscore": 0.8437100052833557, "dann_score": 0.9977665543556213, "dann_rankscore": 0.864329993724823 } ], "dann_snvs": [ { "version": "2014", "dann_score": 0.9977568895535142 } ], "ncbi_clinvar2": [ { "version": "07-Mar-2025", "review_status": "criteria provided, multiple submitters, no conflicts", "review_stars": 2, "variation_id": 12582, "num_submitters": 23, "pub_med_references": [ 7773929, 8439212, 12720172, 15093544, 15696205, 15842656, 16474405, 17332249, 17704260, 17910045, 19047918, 19358724, 20805368, 20949522, 21079152, 22499344, 22683711, 23096712, 23255105, 25695684, 26242988, 26521233, 29298116, 30443000, 30544177, 30902772, 30936194, 31836588, 31891627, 34114335, 35794233 ], "clinical_significance": [ "Likely Pathogenic", "Pathogenic" ], "last_evaluation": "20250201", "origin": null, "accessions": [ { "variation_id": 12582, "accession_id": "RCV005007840", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 1, "diseases": [ { "pub_med": [ 15604628, 18163131, 17508274, 24366376, 24366402, 24432435, 26389210, 26389258, 34242744, 31429903 ], "normalized_disease": [ "Hereditary Breast Carcinoma" ], "symbols": { "omim": "114480", "medgen": "C0346153", "mondo": "MONDO:0016419" }, "names": [ "Hereditary Breast Carcinoma", "Hereditary Breast Carcinoma", "Hereditary Breast Carcinoma" ], "keyword": "Hereditary cancer syndrome", "normalized_cancer": [ "Breast" ], "disease_mechanism": "loss of function" }, { "pub_med": [ 20876176 ], "normalized_disease": [ "Noonan Syndrome 3" ], "symbols": { "orphanet": "648", "omim": "609942", "medgen": "C1860991", "mondo": "MONDO:0012371" }, "names": [ "Noonan Syndrome 3", "Noonan Syndrome 3" ] }, { "normalized_disease": [ "Linear Nevus Sebaceous Syndrome" ], "normalized_cancer": [ "SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME, SOMATIC MOSAIC" ], "symbols": { "orphanet": "2612", "omim": "163200", "medgen": "C4552097", "mondo": "MONDO:0008097", "human_phenotype_ontology": "HP:0010817" }, "names": [ "Linear Nevus Sebaceous Syndrome", "Jadassohn Nevus Phakomatosis", "Linear Nevus Sebaceous Syndrome", "Organoid Nevus Phakomatosis", "Sfm Syndrome", "Linear Nevus Sebaceous Syndrome", "Sebaceous Nevus Syndrome Hemimegalencephaly", "Linear Nevus Sebaceous Syndrome", "Linear Nevus Sebaceous Syndrome", "Linear Sebaceous Nevus Sequence" ] }, { "normalized_disease": [ "Toriello-Lacassie-Droste Syndrome" ], "symbols": { "orphanet": "3339", "omim": "600268", "medgen": "C1838329", "mondo": "MONDO:0010854" }, "names": [ "Toriello-Lacassie-Droste Syndrome", "Toriello-Lacassie-Droste Syndrome", "Aplasia Cutis Congenita Epibulbar Dermoids" ] }, { "normalized_disease": [ "Arteriovenous Malformations of the Brain" ], "symbols": { "orphanet": "46724", "omim": "108010", "medgen": "C0917804", "mondo": "MONDO:0007154", "human_phenotype_ontology": "HP:0002408" }, "names": [ "Arteriovenous Malformations of the Brain", "Cerebral Arteriovenous Malformations", "Arteriovenous Malformations of the Brain" ] }, { "normalized_disease": [ "Urinary Bladder Cancer", "Urinary Bladder Neoplasm", "Childhood Bladder Carcinoma" ], "normalized_cancer": [ "Malignant Tumor", "Bladder/Urinary Tract" ], "symbols": { "omim": "109800", "medgen": "C0005684", "mondo": "MONDO:0001187" }, "names": [ "Urinary Bladder Cancer", "Urinary Bladder Cancer", "Urinary Bladder Neoplasm", "Childhood Bladder Carcinoma" ], "keyword": "Hereditary cancer syndrome" }, { "normalized_disease": [ "Autoimmune Lymphoproliferative Syndrome Type 4" ], "symbols": { "orphanet": "268114", "omim": "614470", "medgen": "C2674723", "mondo": "MONDO:0013767" }, "names": [ "Autoimmune Lymphoproliferative Syndrome Type 4", "Autoimmune Lymphoproliferative Syndrome Type 4", "Autoimmune Lymphoproliferative Syndrome Type 4" ] }, { "pub_med": [ 22138009, 23970018, 32171751 ], "normalized_disease": [ "Acute Myeloid Leukemia" ], "symbols": { "orphanet": "519", "omim": "601626", "medgen": "C0023467", "mesh": "D015470", "mondo": "MONDO:0018874", "human_phenotype_ontology": "HP:0006728" }, "names": [ "Acute Myeloid Leukemia", "Acute Myeloid Leukemia, Adult", "Aml Adult", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Leukemia, Acute Myelogenous, Somatic" ], "normalized_cancer": [ "Acute Myeloid Leukemia", "Acute myelogenous leukemia", "Acute non-lymphocytic leukemia", "Acute granulocytic leukemia", "Leukemia, acute myelogenous, somatic" ], "disease_mechanism": "Constitutively activated FLT3" }, { "normalized_disease": [ "Cardiofaciocutaneous Syndrome 2" ], "symbols": { "orphanet": "1340", "omim": "615278", "medgen": "C3809005", "mondo": "MONDO:0014112" }, "names": [ "Cardiofaciocutaneous Syndrome 2" ] }, { "pub_med": [ 25645574 ], "normalized_disease": [ "Familial Pancreatic Carcinoma" ], "normalized_cancer": [ "Pancreas" ], "symbols": { "omim": "260350", "medgen": "C2931038", "mondo": "MONDO:0015278" }, "names": [ "Familial Pancreatic Carcinoma" ], "keyword": "Hereditary cancer syndrome" }, { "normalized_disease": [ "Gastric Cancer" ], "normalized_cancer": [ "Esophagus/Stomach", "Malignant Tumor" ], "symbols": { "omim": "613659", "medgen": "C0024623", "mesh": "D013274", "mondo": "MONDO:0001056", "human_phenotype_ontology": "HP:0012126" }, "names": [ "Gastric Cancer", "Gastric Cancer", "Gastric Cancer" ] }, { "pub_med": [ 29398453 ], "normalized_disease": [ "Lung Cancer" ], "normalized_cancer": [ "Lung", "Malignant Tumor" ], "symbols": { "omim": "211980", "medgen": "C0242379", "mondo": "MONDO:0008903" }, "names": [ "Lung Cancer", "Lung Cancer", "Lung Cancer" ] } ], "review_date": 20240223, "review_status": "criteria provided, single submitter", "submission_description": [], "submissions": [ { "submitter_date": 20241220, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Fulgent Genetics, Fulgent Genetics", "review_date": 20240223, "method": "clinical testing", "origin": "germline", "diseases": [ { "symbols": { "omim": "108010" } }, { "symbols": { "omim": "109800" } }, { "symbols": { "omim": "114480" } }, { "symbols": { "omim": "163200" } }, { "symbols": { "omim": "211980" } }, { "symbols": { "omim": "260350" } }, { "symbols": { "omim": "600268" } }, { "symbols": { "omim": "601626" } }, { "symbols": { "omim": "609942" } }, { "symbols": { "omim": "613659" } }, { "symbols": { "omim": "614470" } }, { "symbols": { "omim": "615278" } } ], "date_updated": 20250125, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV005634967" } ], "date_created": 20250125, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND multiple conditions", "variant_id": 10190120253982840004 }, { "pub_med_references": [ 29298116 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000585796", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 1, "diseases": [ { "normalized_disease": [ "Arteriovenous Malformations of the Brain" ], "symbols": { "orphanet": "46724", "omim": "108010", "medgen": "C0917804", "mondo": "MONDO:0007154", "human_phenotype_ontology": "HP:0002408" }, "names": [ "Arteriovenous Malformations of the Brain", "Cerebral Arteriovenous Malformations", "Arteriovenous Malformations of the Brain" ] } ], "review_date": 20231103, "review_status": "criteria provided, single submitter", "submission_description": [], "submissions": [ { "submitter_date": 20231212, "submission_description": [ "The KRAS c.35G>A (p.Gly12Asp) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in multiple individuals affected with vascular malformations including numerous individuals with brain arteriovenous malformations (Nikolaev SI et al., PMID: 29298116; Lihua J et al., PMID: 29381910; Al-Olabi et al., PMID: 29461977; Goss JA et al., PMID: 31486960; Schmidt FV et al., PMID: 34114335; Mitchell BJ et al., PMID: 30394973). This variant has been reported in the ClinVar database as a pathogenic/likely pathogenic variant in both a somatic and germline state by multiple submitters (ClinVar ID: 12582) and in numerous cancer cases as a somatic variant in the cancer database COSMIC (COMIC ID: COSV55497369). This variant is only observed on 2/152,128 alleles in the general population (gnomAD v.3.1.2), indicating it is not a common variant. The KRAS c.35G>A (p.Gly12Asp) variant resides within the P-loop region of KRAS that is defined as a critical functional domain (Gelb BD et al., PMID: 29493581). Computational predictors indicate that the variant is damaging, evidence that correlates with impact to KRAS function. In support of this prediction, functional studies show that this variant activates mitogen-activated protein kinase kinase 1 signaling pathway, leading to the formation of vascular malformation (Cistea IC et al., PMID: 23059812; Fish JE et al., PMID: 32552404; Janardhan HP et al., PMID: 32405640). The KRAS gene is defined by the ClinGen's RASopathies expert panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (Gelb BD et al., PMID: 29493581). Based on an internally developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the KRAS c.35G>A (p.Gly12Asp) variant is classified as pathogenic." ], "review_description": "Pathogenic", "submitter_name": "Clinical Genomics Laboratory, Washington University in St. Louis", "review_date": 20231103, "method": "clinical testing", "origin": "somatic", "diseases": [ { "symbols": { "omim": "108010" } } ], "date_updated": 20231224, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV004176950" }, { "submitter_date": 20180306, "submission_description": [ "Using exome DNA sequencing and droplet digital PCR analysis, Nikolaev et al. (2018) identified a gly12-to-asp (G12D, c.35G-A) mutation in a total of 32 of 72 arteriovenous malformations of the brain (BAVM; 108010), and in none of 21 paired blood samples. Patient samples included 39 from a main study group and 33 from an independent validation group. This and the G12V variant (190070.0026) were present in 2.4 to 4.0% of the sequence reads per sample. The G12D mutation drove MAPK-ERK activity in endothelial cells." ], "pub_med_references": [ 29298116 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20180306, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Arteriovenous Malformations of the Brain" ], "normalized_cancer": [ "CNS/Brain" ], "names": [ "Arteriovenous Malformations of the Brain" ] } ], "date_updated": 20180314, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000693723" }, { "submitter_name": "Arin Greene Laboratory, Boston Children's Hospital, Harvard Medical School", "submitter_date": 20190905, "submission_description": [], "review_description": "Pathogenic", "diseases": [ { "symbols": { "omim": "108010" } } ], "date_updated": 20191216, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000992585" } ], "date_created": 20180314, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Cerebral arteriovenous malformation" }, { "variation_id": 12582, "accession_id": "RCV000272938", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 2, "diseases": [ { "symbols": { "medgen": "C3661900" }, "names": [ "Not Provided", "None Provided", "Reclassified - Adra2C Polymorphism", "Reclassified - Adrb1 Polymorphism" ] } ], "review_date": 20231103, "review_status": "criteria provided, multiple submitters, no conflicts", "submission_description": [], "submissions": [ { "submitter_date": 20241108, "submission_description": [ "PP3, PM2, PS3, PS4" ], "review_description": "Pathogenic", "submitter_name": "Mayo Clinic Laboratories, Mayo Clinic", "review_date": 20231103, "method": "clinical testing", "origin": "germline", "diseases": [ { "names": [ "Not Provided" ] } ], "date_updated": 20241124, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV005414064" }, { "submitter_date": 20221228, "submission_description": [ "Reported as a somatic variant in affected tissue from individuals with sebaceous nevi; the variant was not detected in blood or unaffected skin tissue of these individuals (Groesser et al., 2012; Levinsohn et al., 2013; Wang et al., 2015); Observed as a presumably somatic variant associated with malignancies, including various types of leukemia (Paulsson et al., 2008; Koorstra et al., 2008; Tyner et al., 2009; Zhang et al., 2011); Published functional studies demonstrate this variant affects GTP binding activity of the KRAS protein (Chen et al., 2013), and causes an increase in AKT phosphorylation (Petrova et al., 2016); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18813118, 23096712, 23437064, 24803665, 15093544, 19847165, 22264792, 21451123, 21502497, 18308936, 11323676, 26521233, 20805368, 19075190, 21680795, 30394973, 30936194, 30355600, 31836588, 29298116, 32246016, 30443000, 31891627, 33244099, 22683711, 27362559, 17875937, 29493581, 17910045)" ], "review_description": "Pathogenic", "submitter_name": "GeneDx", "review_date": 20221222, "method": "clinical testing", "origin": "germline", "diseases": [ { "names": [ "Not Provided" ] } ], "date_updated": 20221231, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000329383" }, { "submitter_date": 20241213, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "CeGaT Center for Human Genetics Tuebingen", "review_date": 20221201, "method": "clinical testing", "origin": "germline", "diseases": [ { "symbols": { "medgen": "CN517202" } } ], "date_updated": 20241222, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV002821689" }, { "submitter_date": 20220516, "submission_description": [ "This is a recurrent pathogenic variant that has previously been reported in several individuals with sporadic brain arteriovenous malformations (PMID: 29298116, 30902772, 30544177). The c.35G>A variant substitutes the glycine at codon 12 with aspartic acid. Experimental studies suggest that codon 12 substitutions lead to hyperactivation of the KRAS protein (PMID: 29298116)." ], "review_description": "Pathogenic", "submitter_name": "Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital", "review_date": 20210813, "diseases": [ { "names": [ "Not Provided" ] } ], "date_updated": 20220611, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV002525678" }, { "submitter_name": "Department of Pathology and Laboratory Medicine, Sinai Health System", "submitter_date": 20221122, "submission_description": [], "review_description": "Pathogenic", "method": "clinical testing", "origin": "unknown", "diseases": [ { "names": [ "Not Provided" ] } ], "date_updated": 20221129, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV001550138" } ], "date_created": 20161206, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND not provided", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV000548006", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 2, "diseases": [ { "normalized_disease": [ "Rasopathy" ], "symbols": { "medgen": "C5555857", "mondo": "MONDO:0021060" }, "names": [ "Rasopathy", "Rasopathies", "Noonan Spectrum Disorder" ] } ], "review_date": 20221005, "review_status": "criteria provided, multiple submitters, no conflicts", "submission_description": [], "submissions": [ { "submitter_date": 20221110, "submission_description": [ "Variant summary: KRAS c.35G>A (p.Gly12Asp) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249328 control chromosomes (gnomAD). c.35G>A is a well classified pathogenic somatic mutation (ClinVar ID 2582). c.35G>A has been reported with varying levels of somatic mosaicism in individuals affected with anomalous pancreaticobiliary ductal union, epidermal nevus and Keratinocytic epidermal nevi and Schimmelpenning syndrome characterized by nevus sebaceous and extracutaneous abnormalities (Examples: Shimotake_2003, Bourdeaut_2010 and Hafner_2012, Groesser_2012). Experimental evidence have demonstrated that KRAS G12D is embryonically lethal in the mouse model and conditional expression in mouse embryonic fibroblasts causes enhanced proliferation and partial transformation consistent with a gain of function mechanism of disease (example: Tuveson_2004). A different variant affecting the same residue G12S is associated with Cardio-facio-cutaneous syndrome in HGMD (Nava_2007). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic." ], "review_description": "Pathogenic", "submitter_name": "Women's Health and Genetics/Laboratory Corporation of America, LabCorp", "review_date": 20221005, "method": "clinical testing", "origin": "germline", "diseases": [ { "symbols": { "medgen": "CN166718" } } ], "date_updated": 20221119, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV002601600" }, { "submitter_date": 20171005, "submission_description": [ "This sequence change replaces glycine with aspartic acid at codon 12 of the KRAS protein (p.Gly12Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs121913529, ExAC 0.01%). This variant has been reported in the literature as a somatic event (present in tissue from a lesion but not in non-lesional tissue or peripheral blood) in individuals with nevus sebaceous syndrome (PMID: 23255105, 22683711, 23096712, 26521233). It was also observed in a child with epidermal nevus, polycystic kidneys, rhabdomyosarcoma and growth retardation (PMID: 20805368). In one family this variant was found in an infant with severe Schimmelpenning syndrome, whereas the monozygotic twin brother was unaffected showing that this variant in the affected individual was due to a postzygotic somatic event (PMID: 22683711, 23255105). ClinVar contains an entry for this variant (Variation ID: 12582). KRAS p.Gly12Asp is a frequently occurring somatic variant in several different types of cancers, including lung, ovarian, endometrial and pancreatic (PMID: 26861459, 1875403, 24629489, 23174937). Experimental studies using mouse knock-in models have shown that this missense change results in the activation of KRAS and increase in proliferation of mouse embryonic cells. In addition, pancreatic tissue from mice expressing this variant show de-differentiation and activation of signaling factors that initiate pancreatic cancer (PMID: 15093544, 25623042). For these reasons, this variant has been classified as Pathogenic." ], "review_description": "Pathogenic", "submitter_name": "Labcorp Genetics (formerly Invitae), Labcorp", "review_date": 20170630, "method": "clinical testing", "origin": "germline", "diseases": [ { "symbols": { "medgen": "CN166718" } } ], "date_updated": 20171226, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000659085" } ], "date_created": 20171226, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND RASopathy", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV004018620", "allele_id": 27621, "clinical_significance": [ "Likely pathogenic" ], "review_description": "Likely pathogenic", "review_stars": 1, "diseases": [ { "symbols": { "medgen": "CN230736" }, "names": [ "Cardiovascular Phenotype" ] } ], "review_date": 20220822, "review_status": "criteria provided, single submitter", "submission_description": [], "submissions": [ { "submitter_date": 20240424, "submission_description": [ "reported for somatic cases only, for germline findings, please reassess" ], "review_description": "Likely pathogenic", "submitter_name": "Ambry Genetics", "review_date": 20220822, "origin": "germline", "method": "clinical testing", "finding": [ { "symbols": { "medgen": "CN230736" } } ], "date_updated": 20240501, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Likely pathogenic" ], "accession_id": "SCV005023563" } ], "date_created": 20240501, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Cardiovascular phenotype", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV004554600", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 1, "diseases": [ { "names": [ "Congenital Pulmonary Airway Malformations" ] } ], "review_date": 20220719, "review_status": "criteria provided, single submitter", "submission_description": [], "submissions": [ { "submitter_date": 20240515, "submission_description": [ "The c.35G>A variant in KRAS is an established pathogenic variant almost always exclusively found in tissue analysis of individuals with somatic cancers or tissue-limited phenotypes, and it has been deposited in ClinVar [ClinVar ID: 12582] as Pathogenic. The c.35G>A variant is observed in 5 alleles with 0 homozygote in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), which might be due to clonal hematopoesis of indeterminate potential or emerging/existing hematologic malignancies in variant carrying individuals in those databases. The c.35G>A variant in KRAS is located in exon 2 of this 5-exon gene, and is predicted to replace an evolutionarily conserved glycine amino acid with aspartate at position 12 (p.Gly12Asp) in the encoded protein. The p.Gly12Asp variant has been demonstrated to confer oncogenic potential via inhibiting the GTPase activity that result in continuous GTP-bound, active state [PMID: 11323676, 27096871]. Although another variant at codon 12 (p.Gly12Ser) has been reported in the germline of individuals with RASopathy phenotypes [PMID: 17704260, 26242988], p.Gly12Asp variant has not been reported constitutionally. The p.Gly12Asp variant has recently been identified in CPAM sections of individuals at less than 35% variant allele fraction (VAF) while the nearby unaffected lung tissue sections were found to be not carrying the p.Gly12Asp variant [PMID: 35794233]. The c.35G>A variant has been found at 28% VAF (13/47 reads) in this fetal sample, which might reflect the tissue-limited mosaicism of respiratory tract cells present in the amniotic fluid. Based on available evidence this de novo mosaic c.35G>A p.Gly12Asp variant identified in KRAS is classified as Pathogenic." ], "review_description": "Pathogenic", "submitter_name": "New York Genome Center", "review_date": 20220719, "method": "clinical testing", "finding": [ { "symbols": { "hp": "HP:0010959" }, "normalized_phenotype": [ "Congenital Pulmonary Airway Malformation" ] }, { "symbols": { "hp": "HP:0000474" }, "normalized_phenotype": [ "Thickened Nuchal Skin Fold" ] }, { "symbols": { "hp": "HP:0001791" }, "normalized_phenotype": [ "Fetal Ascites" ] } ], "origin": "de novo", "diseases": [ { "names": [ "Congenital Pulmonary Airway Malformations" ] } ], "date_updated": 20240519, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV005044128" } ], "date_created": 20240519, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Congenital Pulmonary Airway Malformations", "variant_id": 10190120253982840004 }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000029215", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 2, "diseases": [ { "normalized_disease": [ "Linear Nevus Sebaceous Syndrome" ], "normalized_cancer": [ "SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME, SOMATIC MOSAIC" ], "symbols": { "orphanet": "2612", "omim": "163200", "medgen": "C4552097", "mondo": "MONDO:0008097", "human_phenotype_ontology": "HP:0010817" }, "names": [ "Linear Nevus Sebaceous Syndrome", "Jadassohn Nevus Phakomatosis", "Linear Nevus Sebaceous Syndrome", "Organoid Nevus Phakomatosis", "Sfm Syndrome", "Linear Nevus Sebaceous Syndrome", "Sebaceous Nevus Syndrome Hemimegalencephaly", "Linear Nevus Sebaceous Syndrome", "Linear Nevus Sebaceous Syndrome", "Linear Sebaceous Nevus Sequence" ] } ], "review_date": 20220322, "review_status": "criteria provided, multiple submitters, no conflicts", "submission_description": [], "submissions": [ { "submitter_date": 20220325, "submission_description": [ "Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000012582). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000012583,VCV000012584, PMID:17704260). The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.875>=0.6, 3CNET: 0.995>=0.75). A missense variant is a common mechanism . The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000040). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline." ], "review_description": "Pathogenic", "submitter_name": "3billion", "review_date": 20220322, "method": "clinical testing", "finding": [ { "symbols": { "hp": "HP:0000618" }, "normalized_phenotype": [ "Blindness" ] }, { "symbols": { "hp": "HP:0002059" }, "normalized_phenotype": [ "Cerebral Atrophy" ] }, { "symbols": { "hp": "HP:0002007" }, "normalized_phenotype": [ "Frontal Bossing" ] }, { "symbols": { "hp": "HP:0002315" }, "normalized_phenotype": [ "Headache" ] }, { "symbols": { "hp": "HP:0002716" }, "normalized_phenotype": [ "Lymphadenopathy" ] }, { "symbols": { "hp": "HP:0010815" }, "normalized_phenotype": [ "Nevus Sebaceous" ] }, { "symbols": { "hp": "HP:0002650" }, "normalized_phenotype": [ "Scoliosis" ] } ], "origin": "germline", "diseases": [ { "symbols": { "omim": "163200" } } ], "date_updated": 20220402, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV002318898" }, { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Linear Nevus Sebaceous Syndrome" ], "normalized_cancer": [ "SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME, SOMATIC MOSAIC" ], "names": [ "Linear Nevus Sebaceous Syndrome" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000051861" }, { "submitter_name": "Equipe Genetique des Anomalies du Developpement, Université de Bourgogne", "submitter_date": 20210614, "submission_description": [], "review_description": "Pathogenic", "method": "clinical testing", "origin": "somatic", "diseases": [ { "symbols": { "omim": "163200" } } ], "date_updated": 20210619, "review_status": "criteria provided, single submitter", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV001736991" } ], "date_created": 20130404, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Linear nevus sebaceous syndrome" }, { "variation_id": 12582, "accession_id": "RCV001799604", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_disease": [ "Capillary Malformation-Arteriovenous Malformation 1" ], "symbols": { "orphanet": "137667", "omim": "608354", "medgen": "C4747394", "mondo": "MONDO:0020783" }, "names": [ "Capillary Malformation-Arteriovenous Malformation 1" ] } ], "review_date": 20210501, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20210629, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Arin Greene Laboratory, Boston Children's Hospital, Harvard Medical School", "review_date": 20210501, "diseases": [ { "symbols": { "omim": "608354" } } ], "date_updated": 20220101, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV001739511" } ], "date_created": 20220101, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Capillary malformation-arteriovenous malformation 1", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV000856666", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_cancer": [ "Ovary/Fallopian Tube" ], "symbols": { "medgen": "C4302356" }, "names": [ "Primary Low Grade Serous Adenocarcinoma Ovary" ] } ], "review_date": 20191104, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20191104, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "University Health Network, Princess Margaret Cancer Centre", "review_date": 20191104, "method": "research", "origin": "somatic", "diseases": [ { "normalized_cancer": [ "Ovary/Fallopian Tube" ], "symbols": { "medgen": "C4302356" }, "names": [ "Primary Low Grade Serous Adenocarcinoma Ovary" ] } ], "date_updated": 20191129, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000999192" } ], "date_created": 20191129, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Primary low grade serous adenocarcinoma of ovary", "variant_id": 10190120253982840004 }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000013411", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "pub_med": [ 17060676, 24493721, 25394175 ], "normalized_disease": [ "Exocrine Pancreatic Carcinoma", "Familial Pancreatic Carcinoma" ], "symbols": { "orphanet": "1333", "medgen": "C0235974", "mesh": "C562463", "mondo": "MONDO:0005192" }, "names": [ "Exocrine Pancreatic Carcinoma", "Pancreatic Acinar Carcinoma", "Exocrine Pancreatic Carcinoma", "Familial Pancreatic Carcinoma", "Familial Pancreatic Carcinoma", "Exocrine Pancreatic Carcinoma" ], "normalized_cancer": [ "Pancreas" ], "disease_mechanism": "loss of function" } ], "review_date": 20190207, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20190211, "submission_description": [ "Variant causes impairment of the intrinsic GTPase activity of KRAS and subsequent activation of downstream signaling pathways that drive cancer growth." ], "review_description": "Pathogenic", "submitter_name": "Laboratory for Clinical Genomics and Advanced Technology, Dartmouth-Hitchcock Medical Center", "review_date": 20190207, "method": "research", "finding": [ { "symbols": { "hp": "HP:0002894" }, "normalized_phenotype": [ "Neoplasm Of The Pancreas" ] } ], "origin": "somatic", "diseases": [ { "symbols": { "omim": "260350" } } ], "date_updated": 20170308, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000882700" }, { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Familial Pancreatic Carcinoma" ], "normalized_cancer": [ "Pancreas" ], "names": [ "Familial Pancreatic Carcinoma" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000033658" } ], "date_created": 20130404, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Carcinoma of pancreas" }, { "variation_id": 12582, "accession_id": "RCV000433573", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "pub_med": [ 22138009, 23970018, 32171751 ], "normalized_disease": [ "Acute Myeloid Leukemia" ], "symbols": { "orphanet": "519", "omim": "601626", "medgen": "C0023467", "mesh": "D015470", "mondo": "MONDO:0018874", "human_phenotype_ontology": "HP:0006728" }, "names": [ "Acute Myeloid Leukemia", "Acute Myeloid Leukemia, Adult", "Aml Adult", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Acute Myeloid Leukemia", "Leukemia, Acute Myelogenous, Somatic" ], "normalized_cancer": [ "Acute Myeloid Leukemia", "Acute myelogenous leukemia", "Acute non-lymphocytic leukemia", "Acute granulocytic leukemia", "Leukemia, acute myelogenous, somatic" ], "disease_mechanism": "Constitutively activated FLT3" } ], "review_date": 20180330, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20210421, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Hematopathology, The University of Texas M.D. Anderson Cancer Center", "review_date": 20180330, "method": "clinical testing", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Acute Myeloid Leukemia" ], "normalized_cancer": [ "Acute Myeloid Leukemia" ], "names": [ "Acute Myeloid Leukemia" ] } ], "date_updated": 20210424, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV001571657" } ], "date_created": 20170308, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Acute myeloid leukemia", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV000662266", "allele_id": 27621, "clinical_significance": [ "Likely pathogenic" ], "review_description": "Likely pathogenic", "review_stars": 0, "diseases": [ { "normalized_cancer": [ "Vascular Tumors Including Pyogenic Granuloma" ], "names": [ "Vascular Tumors Including Pyogenic Granuloma" ] } ], "review_date": 20150219, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20171127, "submission_description": [], "review_description": "Likely pathogenic", "submitter_name": "Yale Center for Mendelian Genomics, Yale University", "review_date": 20150219, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_cancer": [ "Vascular Tumors Including Pyogenic Granuloma" ], "names": [ "Vascular Tumors Including Pyogenic Granuloma" ] } ], "date_updated": 20180714, "review_status": "no assertion criteria provided", "clinical_significance": [ "Likely pathogenic" ], "accession_id": "SCV000784594" } ], "date_created": 20180714, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Vascular Tumors Including Pyogenic Granuloma", "variant_id": 10190120253982840004 }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000144969", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "pub_med": [ 24493721 ], "normalized_disease": [ "Juvenile Myelomonocytic Leukemia" ], "normalized_cancer": [ "Juvenile Myelomonocytic Leukemia" ], "symbols": { "orphanet": "86834", "omim": "607785", "medgen": "C0349639", "mondo": "MONDO:0011908", "human_phenotype_ontology": "HP:0012209" }, "names": [ "Juvenile Myelomonocytic Leukemia", "Juvenile Myelomonocytic Leukemia" ], "keyword": "Hereditary cancer syndrome" } ], "review_date": 20140828, "review_status": "no assertion criteria provided", "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "submissions": [ { "submitter_date": 20160426, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine", "review_date": 20140828, "method": "clinical testing", "origin": "somatic", "diseases": [ { "symbols": { "omim": "607785" } } ], "date_updated": 20160529, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000198478" }, { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Juvenile Myelomonocytic Leukemia" ], "normalized_cancer": [ "Juvenile Myelomonocytic Leukemia" ], "names": [ "Juvenile Myelomonocytic Leukemia" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000191996" } ], "date_created": 20141122, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Juvenile myelomonocytic leukemia" }, { "variation_id": 12582, "accession_id": "RCV000150896", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "pub_med": [ 24868098, 24673736, 24627688, 23667368, 30813707 ], "normalized_disease": [ "Non-Small Cell Lung Carcinoma" ], "symbols": { "medgen": "C0007131", "mesh": "D002289", "mondo": "MONDO:0005233", "human_phenotype_ontology": "HP:0030358" }, "names": [ "Non-Small Cell Lung Carcinoma", "Non-Small Cell Lung Carcinoma" ], "normalized_cancer": [ "Non-Small Cell Lung Cancer" ], "disease_mechanism": "Other" } ], "review_date": 20140828, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20160426, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine", "review_date": 20140828, "method": "clinical testing", "origin": "somatic", "diseases": [ { "symbols": { "medgen": "C0007131" } } ], "date_updated": 20160529, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000198479" }, { "submitter_name": "Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center", "submitter_date": 20190207, "submission_description": [], "review_description": "Pathogenic", "method": "research", "origin": "somatic", "diseases": [ { "symbols": { "hp": "HP:0030358" } } ], "date_updated": 20170308, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000882686" } ], "date_created": 20150130, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Non-small cell lung carcinoma", "variant_id": 10190120253982840004 }, { "variation_id": 12582, "accession_id": "RCV000150897", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "pub_med": [ 19042984, 22964825, 23188549, 33410258, 29450531 ], "normalized_disease": [ "Ovarian Neoplasm" ], "normalized_cancer": [ "Ovary/Fallopian Tube" ], "symbols": { "medgen": "C0919267", "mesh": "D010051", "mondo": "MONDO:0021068", "human_phenotype_ontology": "HP:0100615" }, "names": [ "Ovarian Neoplasm", "Ovarian Neoplasm", "Ovarian Neoplasm", "Ovarian Neoplasms" ] } ], "review_date": 20140828, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20160426, "submission_description": [ "Somatic KRAS variants have been identified in up to 15% of cases of ovarian carcinoma, and Gly12Asp accounts for 40% of the identified KRAS variants (COSMIC 2010; Auner 2009)." ], "review_description": "Pathogenic", "submitter_name": "Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine", "review_date": 20140828, "method": "clinical testing", "origin": "somatic", "diseases": [ { "symbols": { "omim": "167000" } } ], "date_updated": 20160529, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000198480" } ], "date_created": 20150130, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Ovarian neoplasm", "variant_id": 10190120253982840004 }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000029214", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_cancer": [ "NEVUS SEBACEOUS, SOMATIC" ], "symbols": { "medgen": "C3854181", "human_phenotype_ontology": "HP:0010815" }, "names": [ "Nevus Sebaceous", "Nevus Sebaceous, Somatic" ] } ], "review_date": 20121025, "review_status": "no assertion criteria provided", "submission_description": [], "submissions": [ { "submitter_date": 20171101, "submission_description": [], "review_description": "Pathogenic", "submitter_name": "Yale Center for Mendelian Genomics, Yale University", "review_date": 20121025, "method": "literature only", "origin": "somatic", "diseases": [ { "names": [ "Nevus Sebaceous" ] } ], "date_updated": 20151011, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000611562" }, { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_cancer": [ "NEVUS SEBACEOUS, SOMATIC" ], "names": [ "Nevus Sebaceous, Somatic" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000051860" } ], "date_created": 20130404, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Nevus sebaceous" }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000022799", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_disease": [ "Nevus, Epidermal" ], "normalized_cancer": [ "Nevus, epidermal, somatic" ], "symbols": { "orphanet": "79414", "omim": "162900", "medgen": "C0334082", "mondo": "MONDO:0008093", "human_phenotype_ontology": "HP:0010816" }, "names": [ "Nevus, Epidermal", "Nevus, Epidermal", "Nevus, Epidermal" ], "keyword": "Hereditary cancer syndrome" } ], "review_date": 20120610, "review_status": "no assertion criteria provided", "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "submissions": [ { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Nevus, Epidermal" ], "normalized_cancer": [ "EPIDERMAL NEVUS, SOMATIC" ], "names": [ "Nevus, Epidermal" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000044088" } ], "date_created": 20130404, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Epidermal nevus" }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV002508117", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_disease": [ "Gastric Cancer" ], "normalized_cancer": [ "Esophagus/Stomach", "Malignant Tumor" ], "symbols": { "omim": "613659", "medgen": "C0024623", "mesh": "D013274", "mondo": "MONDO:0001056", "human_phenotype_ontology": "HP:0012126" }, "names": [ "Gastric Cancer", "Gastric Cancer", "Gastric Cancer" ] } ], "review_date": 20120610, "review_status": "no assertion criteria provided", "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "submissions": [ { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_disease": [ "Gastric Cancer" ], "normalized_cancer": [ "Esophagus/Stomach" ], "names": [ "Gastric Cancer" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000033659" } ], "date_created": 20230107, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Gastric cancer" }, { "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "variation_id": 12582, "variant_id": 10190120253982840004, "accession_id": "RCV000144970", "allele_id": 27621, "clinical_significance": [ "Pathogenic" ], "review_description": "Pathogenic", "review_stars": 0, "diseases": [ { "normalized_disease": [ "Autoimmune Lymphoproliferative Syndrome Type 4" ], "symbols": { "orphanet": "268114", "omim": "614470", "medgen": "C2674723", "mondo": "MONDO:0013767" }, "names": [ "Autoimmune Lymphoproliferative Syndrome Type 4", "Autoimmune Lymphoproliferative Syndrome Type 4", "Autoimmune Lymphoproliferative Syndrome Type 4" ] } ], "review_date": 20120610, "review_status": "no assertion criteria provided", "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "submissions": [ { "submitter_date": 20220309, "submission_description": [ "Pancreatic Carcinoma, Somatic", "Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.", "Gastric Cancer, Somatic", "Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.", "Epidermal Nevus, Somatic", "Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.", "Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.", "Nevus Sebaceous, Somatic", "Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).", "Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic", "The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.", "Juvenile Myelomonocytic Leukemia, Somatic", "In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.", "RAS-associated Autoimmune Leukoproliferative Disorder, Somatic", "In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene." ], "pub_med_references": [ 7773929, 8439212, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711 ], "review_description": "Pathogenic", "submitter_name": "OMIM", "review_date": 20120610, "method": "literature only", "origin": "somatic", "diseases": [ { "normalized_cancer": [ "RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER, SOMATIC" ], "names": [ "Ras-Associated Autoimmune Leukoproliferative Disorder, Somatic" ] } ], "date_updated": 20220312, "review_status": "no assertion criteria provided", "clinical_significance": [ "Pathogenic" ], "accession_id": "SCV000191997" } ], "date_created": 20141122, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Autoimmune lymphoproliferative syndrome type 4" }, { "variation_id": 12582, "variant_id": 10190120253982840004, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND multiple conditions", "submissions": [ { "submitter_name": "Martignetti Lab, Icahn School of Medicine at Mount Sinai", "submitter_date": 20230913, "submission_description": [], "review_description": "association", "method": "research", "finding": [ { "names": [ "Atypical Endometrial Hyperplasia" ] } ], "origin": "somatic", "diseases": [ { "symbols": { "mondo": "MONDO:0006096" } }, { "symbols": { "mondo": "MONDO:0006193" } } ], "date_updated": 20230916, "review_status": "no assertion criteria provided", "clinical_significance": [ "association" ], "accession_id": "SCV004035006" } ], "submission_description": [], "diseases": [ { "normalized_disease": [ "Endometrial Hyperplasia without Atypia" ], "symbols": { "medgen": "C1516855", "mondo": "MONDO:0006193" }, "names": [ "Endometrial Hyperplasia without Atypia" ] }, { "normalized_disease": [ "Atypical Endometrial Hyperplasia" ], "symbols": { "medgen": "C0349579", "mondo": "MONDO:0006096" }, "names": [ "Atypical Endometrial Hyperplasia" ] } ], "review_stars": 0, "date_created": 20230916, "review_description": "association", "allele_id": 27621, "review_status": "no assertion criteria provided", "clinical_significance": [ "association" ], "accession_id": "RCV003327361" }, { "variation_id": 12582, "variant_id": 10190120253982840004, "title": "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Encephalocraniocutaneous lipomatosis", "submissions": [ { "submitter_name": "GeneReviews", "submitter_date": 20220225, "submission_description": [], "review_description": "not provided", "method": "literature only", "origin": "somatic", "diseases": [ { "symbols": { "medgen": "C0406612" } } ], "date_updated": 20221001, "review_status": "no assertion provided", "clinical_significance": [ "not provided" ], "accession_id": "SCV002099547" } ], "submission_description": [], "diseases": [ { "normalized_disease": [ "Encephalocraniocutaneous Lipomatosis" ], "symbols": { "orphanet": "2396", "omim": "613001", "medgen": "C0406612", "mondo": "MONDO:0013074" }, "names": [ "Encephalocraniocutaneous Lipomatosis" ], "keyword": "Neoplasm" } ], "review_stars": 0, "date_created": 20220303, "review_description": "not provided", "allele_id": 27621, "review_status": "no assertion provided", "clinical_significance": [ "not provided" ], "accession_id": "RCV001839445" } ], "main_data": "likely pathogenic, pathogenic **2**", "names": [ "NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)" ], "variant_type": "SNV" } ], "publications": { "publications": [ { "pub_med_id": 39501138 }, { "pub_med_id": 37772552 }, { "pub_med_id": 37010994 }, { "pub_med_id": 36627374 }, { "pub_med_id": 36523988 }, { "pub_med_id": 36414681 }, { "pub_med_id": 35907592 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 35794233 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 35099867 }, { "pub_med_id": 35075146 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 34820593 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 34723452 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 34114335 }, { "pub_med_id": 33917572 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 33661592 }, { "pub_med_id": 33538228 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 33226740 }, { "pub_med_id": 32903495 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 32810914 }, { "referenced_by": [ "GDC" ], "pub_med_id": 31949278 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 31891627 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 31836588 }, { "pub_med_id": 31649840 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 31409810 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 30936194 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 30902772 }, { "referenced_by": [ "GenCC", "VarSome users", "UniProt Variants" ], "pub_med_id": 30891959 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 30544177 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 30463544 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 30443000 }, { "pub_med_id": 30368666 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 29846100 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 29721857 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 29575536 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 29525983 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 29298116 }, { "pub_med_id": 28797274 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 27959684 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 27872090 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 27221540 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 27154293 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 27123948 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 27010960 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 26521233 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 26372703 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 26352686 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 26242988 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 26161928 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 25695684 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 25553307 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 25157968 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 25044103 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 24868098 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 24673736 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 24265155 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 24225759 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 23946963 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 23619274 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 23565280 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 23524406 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 23497191 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 23406027 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 23255105 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 23182985 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 23096712 }, { "referenced_by": [ "cBioPortal", "GDC", "UniProt Variants", "CIViC" ], "pub_med_id": 23014527 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 22948721 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 22918138 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 22897852 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 22683711 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 22499344 }, { "referenced_by": [ "cBioPortal", "GDC", "VarSome users" ], "pub_med_id": 22407852 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 22392911 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 22282465 }, { "pub_med_id": 22266220 }, { "pub_med_id": 22247021 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 22246397 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 22235099 }, { "referenced_by": [ "cBioPortal", "GDC", "UniProt Variants", "CIViC" ], "pub_med_id": 22025163 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 21975775 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 21398618 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 21348050 }, { "pub_med_id": 21285991 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 21228335 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 21169357 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 21079152 }, { "referenced_by": [ "UniProt Variants" ], "pub_med_id": 20963938 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 20949522 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 20921465 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 20921462 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 20805368 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 20619739 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 20609353 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19881948 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19794967 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19773371 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19679400 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC" ], "pub_med_id": 19358724 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 19284554 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19255327 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 19223544 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19114683 }, { "referenced_by": [ "VarSome users" ], "pub_med_id": 19087308 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19075190 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC" ], "pub_med_id": 19047918 }, { "referenced_by": [ "cBioPortal", "GDC", "UniProt Variants", "CIViC" ], "pub_med_id": 19029981 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 19018267 }, { "referenced_by": [ "cBioPortal", "GDC", "CIViC" ], "pub_med_id": 18794081 }, { "referenced_by": [ "cBioPortal", "GDC", "UniProt Variants", "CIViC" ], "pub_med_id": 18316791 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC" ], "pub_med_id": 17910045 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC" ], "pub_med_id": 17704260 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 17409929 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 17384584 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants", "dbNSFP" ], "pub_med_id": 17332249 }, { "referenced_by": [ "cBioPortal", "GDC", "CIViC" ], "pub_med_id": 16618717 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 16533793 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 16497971 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp", "ClinVar", "CGD", "dbNSFP" ], "pub_med_id": 16474405 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 16434492 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 16361624 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC" ], "pub_med_id": 15842656 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "CIViC" ], "pub_med_id": 15696205 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 15093544 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 14534542 }, { "referenced_by": [ "ClinVar" ], "pub_med_id": 12720172 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 12483530 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 12460918 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 11050000 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 8439212 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants", "dbNSFP" ], "pub_med_id": 7773929 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 3122217 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 3034404 }, { "referenced_by": [ "cBioPortal", "GDC" ], "pub_med_id": 2278970 } ], "genes": [ { "publications": [ { "referenced_by": [ "CIViC" ], "pub_med_id": 32822286 }, { "referenced_by": [ "GenCC", "VarSome users", "UniProt Variants" ], "pub_med_id": 30891959 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 30847515 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 28525386 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 28492898 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 28275037 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 28259530 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 27876675 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 27502722 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 27217383 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 27167191 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 27037411 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26881434 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26802155 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26725216 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26709701 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26666244 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26307133 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 26209642 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 26161928 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 25968887 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 25808193 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 25722381 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 25322874 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 25294897 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 25199829 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24947927 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24915778 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24685132 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24642870 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 24623306 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24571676 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24559322 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 24265155 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 24166148 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23934108 }, { "referenced_by": [ "CGD" ], "pub_med_id": 23885229 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 23875798 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23828442 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 23698361 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23435671 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23434733 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23200175 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 23099803 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 23059812 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22810899 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22805291 }, { "referenced_by": [ "CGD" ], "pub_med_id": 22777296 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 22711838 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 22683711 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22586653 }, { "referenced_by": [ "CGD" ], "pub_med_id": 22510777 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 22499344 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 22488932 }, { "referenced_by": [ "CGD" ], "pub_med_id": 22211815 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22180495 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22169769 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 22025157 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21985784 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21969500 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21890455 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 21871821 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21862683 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21847063 }, { "referenced_by": [ "GenCC", "CGD", "dbNSFP" ], "pub_med_id": 21797849 }, { "referenced_by": [ "GenCC", "PanelApp" ], "pub_med_id": 21396583 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 21258250 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 21079152 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 21063026 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 20956938 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 20949621 }, { "referenced_by": [ "PanelApp", "cBioPortal", "ClinVar", "GDC", "UniProt Variants" ], "pub_med_id": 20805368 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 20619739 }, { "referenced_by": [ "CGD" ], "pub_med_id": 20602484 }, { "referenced_by": [ "CGD" ], "pub_med_id": 20358587 }, { "referenced_by": [ "GenCC", "CGD" ], "pub_med_id": 20301365 }, { "referenced_by": [ "CGD" ], "pub_med_id": 20301303 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 20038723 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 19934290 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 19903786 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 19603024 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp", "CGD", "dbNSFP" ], "pub_med_id": 19396835 }, { "referenced_by": [ "UniProt Variants", "CIViC" ], "pub_med_id": 19223544 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 18946061 }, { "referenced_by": [ "cBioPortal", "GDC", "CIViC" ], "pub_med_id": 18794081 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 18528420 }, { "referenced_by": [ "CGD" ], "pub_med_id": 18456719 }, { "referenced_by": [ "cBioPortal", "GDC", "UniProt Variants", "CIViC" ], "pub_med_id": 18316791 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 18202412 }, { "referenced_by": [ "CGD" ], "pub_med_id": 18042262 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 17601930 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 17590872 }, { "referenced_by": [ "PanelApp", "CGD", "dbNSFP" ], "pub_med_id": 17468812 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants", "dbNSFP" ], "pub_med_id": 17332249 }, { "referenced_by": [ "GenCC", "CGD", "dbNSFP" ], "pub_med_id": 17056636 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 16825433 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp", "dbNSFP" ], "pub_med_id": 16773572 }, { "referenced_by": [ "cBioPortal", "GDC", "CIViC" ], "pub_med_id": 16618717 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 16533793 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp", "ClinVar", "CGD", "dbNSFP" ], "pub_med_id": 16474405 }, { "referenced_by": [ "GenCC", "PanelApp", "CGD", "dbNSFP" ], "pub_med_id": 16474404 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 16247081 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "CIViC" ], "pub_med_id": 15696205 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 15597105 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 14699048 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 14534542 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 12176867 }, { "referenced_by": [ "CIViC" ], "pub_med_id": 11208838 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 8955068 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 7949098 }, { "referenced_by": [ "cBioPortal", "ClinVar", "GDC", "UniProt Variants", "dbNSFP" ], "pub_med_id": 7773929 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 6695174 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 6092920 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 3627975 }, { "referenced_by": [ "UniProt Variants", "dbNSFP" ], "pub_med_id": 3034404 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 1553789 } ], "gene_symbol": "KRAS", "gene_id": 12340 } ] }, "publication_counts": [ { "type": "variant", "id": "10190120253982840004", "count": 1871 }, { "type": "gene", "id": 12340, "count": 14067, "symbol": "KRAS" } ], "uniprot_variants": [ { "version": "07-Feb-2025", "items": [ { "annotation_id": "VAR_016026", "protein_id": "G3V4K2", "proteinname": "KRAS proto-oncogene, GTPase", "somaticstatus": "False", "frequency": null, "gene": "KRAS", "clinicalsignificances": [ "Pathogenic", "Disease" ], "transcripts": [ "ENST00000556131" ], "association": [ { "disease": "Acute myeloid leukemia ", "disease_description": "A clonal expansion of myeloid blasts in the bone marrow, blood or other tissues.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 20963938, 33226740, 33661592, 34723452 ], "cosmic_study": null } }, { "disease": "Atypical endometrial hyperplasia", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Autoimmune lymphoproliferative syndrome type 4", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Capillary malformation-arteriovenous malformation 1 ", "disease_description": "Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations mostly localized on the face and limbs.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 21348050 ], "cosmic_study": null } }, { "disease": "Carcinoma of pancreas", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Cerebral arteriovenous malformation ", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Colorectal Cancer", "disease_description": "While the KRAS G12 region is a widely studied recurrent region in cancer, its impact on clinical action is still actively debated. Often associated with tumors that are wild-type for other drivers (EGFR and ALK specifically), the prognosis for patients with this mutation seems to be worse than the KRAS wild-type cohort in patients with colorectal and pancreatic cancer, however this hypothesis is in need of further validation. This mutation, along with the mutations affecting the neighboring G13 position, may result in a less responsive tumor when treated with first-generation TKI's like gefitinib. The NCCN guidelines for colorectal cancer contain recommendations that the targeted therapies cetuximab and panitumumab should only be used in the context of wild type KRAS. However, cetuximab treatment was shown to extend survival in a single cohort of colorectal patients with G12D mutations. Overall, the interpretation for KRAS mutations in most clinical scenarios is still undecided.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 11050000, 12483530, 16497971, 17409929, 18316791, 19029981, 19223544, 19284554, 20619739, 22025163, 22246397, 22392911, 22948721, 23014527, 23524406, 23565280, 24265155, 26161928, 26352686, 27010960, 27959684 ], "cosmic_study": null } }, { "disease": "Congenital Pulmonary Airway Malformations", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Encephalocraniocutaneous lipomatosis ", "disease_description": "Encephalocraniocutaneous lipomatosis (ECCL) comprises a spectrum of predominantly congenital anomalies.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 35099867 ], "cosmic_study": null } }, { "disease": "Endometrial hyperplasia without atypia", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Epidermal nevus", "disease_description": "PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 23946963 ], "cosmic_study": null } }, { "disease": "Gastric cancer", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Gastric cancer ", "disease_description": "A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 3034404, 7773929, 14534542 ], "cosmic_study": null } }, { "disease": "Juvenile myelomonocytic leukemia ", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Leukemia, juvenile myelomonocytic ", "disease_description": "An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 17332249 ], "cosmic_study": null } }, { "disease": "Linear nevus sebaceous syndrome", "disease_description": "Schimmelpenning-Feuerstein-Mims syndrome, also known as linear sebaceous nevus syndrome, is characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects (summary by Happle, 1991 and Ernst et al.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Lung carcinoma", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Neoplasm", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 22918138, 23619274 ], "cosmic_study": null } }, { "disease": "Neoplasm of the large intestine", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Non-small cell lung carcinoma ", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 24673736, 24868098 ], "cosmic_study": null } }, { "disease": "Ovarian neoplasm", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Primary low grade serous adenocarcinoma of ovary", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "RASopathy", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Schimmelpenning-Feuerstein-Mims syndrome ", "disease_description": "A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.", "disease_symbol": null, "disease_alt_symbol": null, "evidences": { "pub_med_references": [ 30891959 ], "cosmic_study": null } }, { "disease": "Thyroid tumor", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} }, { "disease": "Vascular Tumors Including Pyogenic Granuloma", "disease_description": null, "disease_symbol": null, "disease_alt_symbol": null, "evidences": {} } ], "siftscore": null, "siftprediction": null, "polyphenscore": null, "polyphenprediction": null, "evidences": { "pub_med_references": [ 7773929, 8439212, 16533793, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711, 29298116, 30891959, 34820593 ], "cosmic_study": [] }, "xrefs": { "cosmicmutationid": [ "COSV55497369", "COSV55865099" ], "clinvaraccession": [] }, "variant_type": "Disease", "disease": "Acute myeloid leukemia ", "disease_symbol": null, "disease_alt_symbol": null, "bed_comments": null, "pub_med_references": [ 7773929, 8439212, 16533793, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711, 29298116, 30891959, 34820593 ] } ] } ], "wustl_civic": [ { "version": "08-Dec-2023", "items": [ { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Lung Non-small Cell Carcinoma", "doid": "3908", "drug_interaction_type": null, "drugs": [ "Dabrafenib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/91", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "In a patient with V600E-positive NSCLC, KRAS G12D seemed to confer resistance to dabrafenib.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-11-24 19:49:00 UTC", "nct_ids": null, "normalized_drug": [ "Dabrafenib" ], "phenotypes": null, "pub_med_references": [ 23524406 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": "CA122538", "variant_groups": [ { "group": "EGFR TKI Resistance", "group_details": { "description": "EGFR pathway activation is a nearly ubiquitous hallmark of cancer. Many tyrosine kinase inhibitors have been developed to target EGFR pathway activity. One such inhibitor, erlotinib, has demonstrated efficacy in an EGFR over-active setting. However, the T790M missense mutation has shown to confer resistance to this inhibitor in cell lines and case studies.", "variant_group_civic_url": "https://civicdb.org/links/variant_groups/12" } } ], "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Positive", "disease": "Lung Cancer", "doid": "1324", "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/228", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "KRAS G12D mutation occurs in never smokers significantly more often than in smokers.", "evidence_status": "accepted", "evidence_type": "Diagnostic", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 23014527 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Sensitivity/Response", "disease": "Lung Non-small Cell Carcinoma", "doid": "3908", "drug_interaction_type": null, "drugs": [ "Selumetinib", "Dactolisib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/305", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "The use of NVP-BEZ235 in conjunction with ARRY-142886, but not as monotherapy, in a lung cancer model with KRAS G12D mutation led to marked tumor regression.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Dactolisib", "Selumetinib" ], "phenotypes": null, "pub_med_references": [ 19029981 ], "rating": "4", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Sensitivity/Response", "disease": "Pancreatic Carcinoma", "doid": "4905", "drug_interaction_type": null, "drugs": [ "Akt Inhibitor MK2206" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/937", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "Among 33 patients treated with pan-AKT inhibitor MK-2206 in this phase 1 study, one patient with pancreatic adenocarcinoma and PTEN loss and a KRAS G12D mutation experienced a decrease of approximately 60% in cancer antigen 19-9 levels and 23% shrinkage in tumor measurements.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Akt Inhibitor Mk2206" ], "phenotypes": null, "pub_med_references": [ 22025163 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Better Outcome", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1215", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "In 119 metastatic colorectal cancer patients treated with cetuximab-based first-line chemotherapy, KRAS G12D mutations (N=44) were associated with longer overall patient survival when compared to other KRAS G12 mutations (23.3 vs 14-18 months; G12V, A, C, S, R).", "evidence_status": "accepted", "evidence_type": "Prognostic", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 22948721 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Poor Outcome", "disease": "Pancreatic Cancer", "doid": "1793", "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1300", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "In 219 patients with metastatic pancreatic ductal adenocarcinoma, a multivariate analysis identified KRAS G12D mutations as an independent predictor of poorer prognosis both in patients that have received chemotherapy (N=49/162), and the entire series (N=73/219). HR of 1.84 (P=0.02) and 1.44 (P=0.01), respectively.", "evidence_status": "accepted", "evidence_type": "Prognostic", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 27010960 ], "rating": "4", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Poor Outcome", "disease": "Malignant Exocrine Pancreas Neoplasm", "doid": "1795", "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1311", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "In 171 patients with tumors of the exocrine pancreas, a KRAS G12D mutation (N=60) was associated with shorter overall survival than being wild-type for KRAS (N=21; Hazard Ratio: 95% CI between 1.14 and 2.67). Additionally, KRAS mutations combined with CDKN2A alterations (N=26) showed an even worse OS than those wild-type for both (N=17; HR: 95%CI 1.33-7.10).", "evidence_status": "accepted", "evidence_type": "Prognostic", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 23565280 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Hairy Cell Leukemia", "doid": "285", "drug_interaction_type": null, "drugs": [ "Vemurafenib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1580", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "One patient enrolled in a clinical study to evaluate vemurafenib treatment of BRAF V600E mutant hairy-cell leukemia developed resistance to vemurafenib retreatment. 300-gene targeted sequencing of the patient’s genome revealed activating subclonal KRAS mutations (KRAS G12D, 15.2% allele frequency; KRAS K117N, 1.2%), as well as a RUNX1 A55E mutation (5.9%) that had not been seen prior to vemurafenib treatment or at remission. BRAF V600E allele frequency was detectable (2.4%) at the time of remission but dramatically increased at relapse (64.9%).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": [ "NCT01711632" ], "normalized_drug": [ "Vemurafenib" ], "phenotypes": null, "pub_med_references": [ 26352686 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Poor Outcome", "disease": "Pancreatic Ductal Carcinoma", "doid": "3587", "drug_interaction_type": null, "drugs": null, "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1732", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "Exon-2 KRAS mutation status was analyzed in 219 patients with pancreatic ductal carcinoma, excluding those who had previously undergone chemotherapy, first-line pancreatic resection, or neoadjuvant treatment with chemotherapy or radiotherapy. 72 patients had wild-type KRAS, 147 had a codon-12 KRAS mutation (G12D, G12V, or G12R) and 73 had a G12D KRAS mutation, specifically. There was no significant difference in overall survival between wild-type patients and patients with any type of exon-12 mutation. However, patients with the G12D mutation exhibited significantly lower overall survival compared to wild-type patients in univariate and multivariate analyses. This difference in overall survival between wild-type and G12D patients persisted in the subset of patients who underwent chemotherapy at any point after enrollment.", "evidence_status": "accepted", "evidence_type": "Prognostic", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 27010960 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Sensitivity/Response", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Therapeutic Tumor Infiltrating Lymphocytes" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/1898", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "A patient with metastatic colorectal cancer was enrolled in a phase 2 clinical trial (NCT01174121). 24 cultures of tumor-infiltrating lymphocytes were expanded from 3 lung metastasis resections. After cultures were tested for reactivity, the patient was infused with 1.48 x 10^11 tumor-infiltrating lymphocytes (75% CD8+ T cells) that were specifically reactive to KRAS G12D. All 7 metastatic lung lesions regressed 40 days after therapy, and the patient had a 9-month partial response.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": null, "phenotypes": null, "pub_med_references": [ 27959684 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Panitumumab" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2193", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "One patient participating in a large retrospective study of EGFR monoclonal antibodies in metastatic, treatment refractory colorectal cancer had a tumor which harbored KRAS G12D, was wildtype for NRAS, BRAF and PIK3CA, and had individual response data. This patient was was a 55 year old female treated with panitumumab monotherapy as 3rd line therapy who experienced progressive disease (PFS: 8 weeks; OS: 9 weeks).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Panitumumab" ], "phenotypes": null, "pub_med_references": [ 20619739 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Cetuximab" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2207", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 76 patients harbored KRAS G12D, were BRAF, NRAS and PIK3CA wt, and had individual response data. Five patients had partial response, 34 had stable disease, and 37 progressed. Treatments included cetuximab + irinotecan (n=61), cetuximab + FOLFIRI (n=6), cetuximab monotherapy (n=5), cetuximab + oxaliplatin + 5FU (n=2), cetuximab + 5FU (n=1), cetuximab + oxaliplatin + bevacizumab (n=1). Median PFS was 12 weeks (3-169 weeks), median OS was 31 weeks (6-232 weeks), and median number of previous chemotherapy lines was 2 (0-5). Median age was 62 years old (32-86), and there were 43 males and 33 females. Using these data and data from the larger cohort, authors concluded that KRAS mutation was strongly associated with poor response to cetuximab and suggested that mutation status of KRAS is the most informative compared to BRAF, NRAS, and PIK3CA exon 20 for predicting cetuximab response.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Cetuximab" ], "phenotypes": null, "pub_med_references": [ 20619739 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Sensitivity/Response", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Selumetinib", "Dactolisib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2218", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring KRAS, NRAS, BRAF or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabilization. Mean tumor growth was lower in the tumors treated with AZD6244+ BEZ235 (+77% vs. +267%, P=1E-6) compared to AZD6244 alone and (+77% vs. +222%, P=0.0014) BEZ235 alone. 32/40 tumors studied had KRAS mutations with 9 G12D (2 with PIK3CA H1047R) and 13 other G12 mutations.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Dactolisib", "Selumetinib" ], "phenotypes": null, "pub_med_references": [ 22392911 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Panitumumab" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2236", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced response to panitumumab compared to wildtype KRAS (HR:0.99, 95% CI:0.73-1.36 vs. HR:0.45, 95% CI:0.34-0.59; P<0.0001). Additionally, patients with KRAS mutations showed no significant improvement between treatment with panitumumab and best supportive care alone (PFS: 7.4 wk vs 7.3 wk).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": [ "NCT00113763", "NCT00113776" ], "normalized_drug": [ "Panitumumab" ], "phenotypes": null, "pub_med_references": [ 18316791 ], "rating": null, "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Lung Cancer", "doid": "1324", "drug_interaction_type": null, "drugs": [ "Gefitinib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2240", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib, patients with KRAS mutations had a lower frequency of partial response (PR) and stable disease (SD) and a higher rate of progressive disease (PD) (PR:0, SD:1, PD:15 vs. PR:24, SD:8, PD:14; P=0.0274) compared to wildtype KRAS patients. Patients with KRAS mutations also had a shorter overall survival compared to wildtype KRAS patients (HR:2.542, 95% CI:1.048-6.168, P=0.0390).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Gefitinib" ], "phenotypes": null, "pub_med_references": [ 17409929 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Multiple Myeloma", "doid": "9538", "drug_interaction_type": null, "drugs": [ "Melphalan" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2247", "evidence_direction": "Supports", "evidence_level": "B", "evidence_statement": "In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were less likely to have a positive response than those with wildtype KRAS (26.9% vs. 58.3%, P=0.015).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Melphalan" ], "phenotypes": null, "pub_med_references": [ 19284554 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Multiple Myeloma", "doid": "9538", "drug_interaction_type": null, "drugs": [ "Melphalan" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2250", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in comparison to cells with wildtype RAS.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Melphalan" ], "phenotypes": null, "pub_med_references": [ 11050000 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Multiple Myeloma", "doid": "9538", "drug_interaction_type": null, "drugs": [ "Melphalan" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2251", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in comparison to cells with wildtype RAS.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Melphalan" ], "phenotypes": null, "pub_med_references": [ 12483530 ], "rating": null, "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Multiple Myeloma", "doid": "9538", "drug_interaction_type": null, "drugs": [ "Melphalan" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/2252", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in comparison to cells with wildtype RAS.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Melphalan" ], "phenotypes": null, "pub_med_references": [ 16497971 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Regorafenib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/3946", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12D mutation demonstrated resistance to regorafenib treatment (IC50: 195.01nM vs. 114.28 nM P<0.01) compared to SW48 cells expressing KRAS wild-type. Resistance was determined by assessing cell viability. Authors concluded that KRAS G12D was more resistant to regorafenib than KRAS wt, and intermediately resistant compared to other common KRAS G12/G13 mutations.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Regorafenib" ], "phenotypes": null, "pub_med_references": [ 26161928 ], "rating": "1", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Melanoma", "doid": "1909", "drug_interaction_type": null, "drugs": [ "Vemurafenib" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/3957", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In vitro studies of M229 (a human melanoma cell line) endogenously expressing wildtype KRAS and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells virally induced to stably over-express KRAS4a G12D or KRAS4b G12D were more resistant to vemurafenib (a BRAF inhibitor) than cells transduced with empty vectors (90% vs 10% survival).", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Vemurafenib" ], "phenotypes": null, "pub_med_references": [ 24265155 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Ovarian Cancer", "doid": "2394", "drug_interaction_type": null, "drugs": [ "Cetuximab" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/3958", "evidence_direction": "Supports", "evidence_level": "D", "evidence_statement": "In an in vitro study, a MCAS cell line expressing KRAS G12D mutation was associated with reduced sensitivity to cetuximab treatment as compared to RMUG-L and OMC-1 cells expressing wild-type KRAS. Resistance was determined by assessing cell growth. Further, in an in vivo experiment, KRAS G12D expressing MCAS xenografts in nude mice had reduced response to cetuximab, as compared to KRAS wild-type expressing RMUG-L xenografts. Resistance was determined by assessing tumor growth.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Cetuximab" ], "phenotypes": null, "pub_med_references": [ 22246397 ], "rating": "3", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null }, { "asco_entry": null, "clinical_significance": "Resistance", "disease": "Colorectal Cancer", "doid": "9256", "drug_interaction_type": null, "drugs": [ "Panitumumab", "Cetuximab" ], "entrez_id": null, "evidence_civic_url": "https://civicdb.org/links/evidence_items/6316", "evidence_direction": "Supports", "evidence_level": "C", "evidence_statement": "In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS, PIK3CA, and PTEN were tested for mutation; KRAS G12D was the only variant noted in the primary tumor of two patients who experienced stable disease following treatment (Patients 22 and 36; colon and rectum tumors; Supplemental Table 1). In the larger cohort, patients with tumors harboring any KRAS mutation had significantly decreased incidence of objective response than patients with wtKRAS tumors. Authors noted that patients with tumors harboring KRAS mutations tended to have decreased PFS and OS compared to those with wild-type tumors though the differences were not statistically significant.", "evidence_status": "accepted", "evidence_type": "Predictive", "gene": "KRAS", "gene_civic_url": null, "last_review_date": "2023-01-09 21:46:27 UTC", "nct_ids": null, "normalized_drug": [ "Cetuximab, Panitumumab" ], "phenotypes": null, "pub_med_references": [ 19223544 ], "rating": "2", "representative_transcript": null, "transcripts": null, "variant": "G12D", "variant_civic_url": null, "variant_origin": "Somatic", "variant_summary": null, "assertion_details": null, "civic_variant_evidence_score": null, "variant_groups": null, "molecular_profile_civic_url": "https://civicdb.org/links/molecular_profiles/79", "molecular_profiles": null } ] } ], "nih_gdc": [ { "version": "08-Dec-2023", "sex": [ { "key": "Female", "value": 61 }, { "key": "Male", "value": 53 } ], "age_freq": [ { "key": "60-70", "value": 36 }, { "key": "70-80", "value": 31 }, { "key": "50-60", "value": 25 }, { "key": "40-50", "value": 10 }, { "key": "80-90", "value": 10 }, { "key": "30-40", "value": 1 }, { "key": "90-100", "value": 1 } ], "os_status": [ { "key": "Living", "value": 102 }, { "key": "Deceased", "value": 12 } ], "race": [ { "key": "European (non-Finnish)", "value": 73 }, { "key": "African", "value": 11 }, { "key": "Latino", "value": 2 }, { "key": "Other", "value": 1 } ], "tumor_status": [ { "key": "Disease Free", "value": 65 }, { "key": "Recurred", "value": 38 } ], "tumor_tissue_site": null, "path_t_stage": [ { "key": "T3", "value": 54 }, { "key": "T2", "value": 9 }, { "key": "T4", "value": 7 }, { "key": "T1", "value": 5 }, { "key": "T4A", "value": 3 }, { "key": "T4B", "value": 3 }, { "key": "T1A", "value": 2 }, { "key": "T1B", "value": 2 }, { "key": "T1B1", "value": 1 }, { "key": "T1C", "value": 1 }, { "key": "T2B", "value": 1 } ], "path_n_stage": [ { "key": "N0", "value": 45 }, { "key": "N1", "value": 21 }, { "key": "N2", "value": 11 }, { "key": "N1B", "value": 3 }, { "key": "Nx", "value": 3 }, { "key": "N1A", "value": 2 }, { "key": "N1C", "value": 1 }, { "key": "N2B", "value": 1 } ], "path_m_stage": [ { "key": "M0", "value": 58 }, { "key": "Mx", "value": 14 }, { "key": "M1", "value": 11 }, { "key": "M1A", "value": 2 } ], "clin_t_stage": [ { "key": "T1", "value": 1 }, { "key": "T1A", "value": 1 } ], "clin_n_stage": [ { "key": "N0", "value": 1 }, { "key": "Nx", "value": 1 } ], "clin_m_stage": [ { "key": "M0", "value": 2 } ], "ajcc_pathologic_tumor_stage": [ { "key": "Stage Iia", "value": 17 }, { "key": "Stage Ii", "value": 11 }, { "key": "Stage I", "value": 10 }, { "key": "Stage Iv", "value": 10 }, { "key": "Stage Iib", "value": 8 }, { "key": "Stage Iiib", "value": 8 }, { "key": "Stage Iii", "value": 5 }, { "key": "Stage Ia", "value": 4 }, { "key": "Stage Iva", "value": 4 }, { "key": "Stage Iiia", "value": 3 }, { "key": "Stage Iiic", "value": 3 }, { "key": "Stage Ib", "value": 1 } ], "total_samples": 203, "study_name": null, "prior_dx": [ { "key": "No", "value": 100 }, { "key": "Yes", "value": 10 }, { "key": "Yes, History Of Synchronous/Bilateral Malignancy", "value": 1 } ], "drug": null, "measure_of_response": [ { "key": "Complete Response", "value": 18 }, { "key": "Clinical Progressive Disease", "value": 6 }, { "key": "Stable Disease", "value": 5 } ], "therapy_type": [ { "key": "Chemotherapy", "value": 99 }, { "key": "Other, Specify In Notes", "value": 13 }, { "key": "Targeted Molecular Therapy", "value": 9 }, { "key": "Ancillary", "value": 3 }, { "key": "Hormone Therapy", "value": 1 } ], "route_of_administration": [ { "key": "Iv", "value": 74 }, { "key": "Po", "value": 10 }, { "key": "Ih", "value": 1 }, { "key": "Im", "value": 1 }, { "key": "Sc", "value": 1 } ], "therapy_ongoing": [ { "key": "NO", "value": 111 }, { "key": "YES", "value": 12 } ], "clinical_significance": [ { "key": "Likely Pathogenic", "value": 203 }, { "key": "Pathogenic", "value": 203 } ], "pub_med_references": [ 2278970, 3122217, 7773929, 8439212, 12460918, 15696205, 15842656, 16361624, 16434492, 16618717, 17332249, 17384584, 17704260, 17910045, 18316791, 18794081, 19018267, 19029981, 19047918, 19075190, 19114683, 19255327, 19358724, 19679400, 19773371, 19794967, 19881948, 20609353, 20805368, 20921462, 20921465, 20949522, 21079152, 21169357, 21228335, 21398618, 21975775, 22025163, 22235099, 22282465, 22407852, 22499344, 22683711, 22897852, 23014527, 23182985, 23406027, 25044103, 25157968, 26372703, 27872090, 29298116, 29525983, 29721857, 30463544, 31949278 ], "oncotree_code": [ { "key": "COAD", "value": 38 }, { "key": "BOWEL", "value": 11 }, { "key": "PANCREAS", "value": 9 }, { "key": "READ", "value": 8 }, { "key": "LUNG", "value": 7 }, { "key": "LAIS", "value": 4 }, { "key": "STOMACH", "value": 4 }, { "key": "GBM", "value": 3 }, { "key": "KIDNEY", "value": 2 }, { "key": "STAD", "value": 2 }, { "key": "CERVIX", "value": 1 } ], "cancer_name": [ { "key": "Colon Adenocarcinoma", "value": 38 }, { "key": "Endometrioid endometrial adenocarcinoma", "value": 23 }, { "key": "Colon Mucinous Adenocarcinoma", "value": 9 }, { "key": "Pancreas-Adenocarcinoma Ductal Type", "value": 9 }, { "key": "Rectal Adenocarcinoma", "value": 8 }, { "key": "Lung Adenocarcinoma Mixed Subtype", "value": 5 }, { "key": "Lung Adenocarcinoma- Not Otherwise Specified (NOS)", "value": 4 }, { "key": "Untreated primary (de novo) GBM", "value": 3 }, { "key": "Kidney Papillary Renal Cell Carcinoma", "value": 2 }, { "key": "Rectal Mucinous Adenocarcinoma", "value": 2 }, { "key": "Stomach, Adenocarcinoma, Not Otherwise Specified (NOS)", "value": 2 }, { "key": "Stomach, Intestinal Adenocarcinoma, Not Otherwise Specified (NOS)", "value": 2 }, { "key": "Lung Bronchioloalveolar Carcinoma Nonmucinous", "value": 1 }, { "key": "Lung Papillary Adenocarcinoma", "value": 1 }, { "key": "Infiltrating Ductal Carcinoma", "value": 1 }, { "key": "Stomach, Intestinal Adenocarcinoma, Mucinous Type", "value": 1 }, { "key": "Stomach, Intestinal Adenocarcinoma, Papillary Type", "value": 1 }, { "key": "Endocervical Type of Adenocarcinoma", "value": 1 } ], "cancer_type": [ { "key": "Colorectal Cancer", "value": 46 }, { "key": "Endometrioid endometrial adenocarcinoma", "value": 23 }, { "key": "Bowel Cancer, NOS", "value": 11 }, { "key": "Pancreatic Cancer, NOS", "value": 9 }, { "key": "Lung Cancer, NOS", "value": 7 }, { "key": "Esophageal/Stomach Cancer, NOS", "value": 4 }, { "key": "Non-Small Cell Lung Cancer", "value": 4 }, { "key": "Glioma", "value": 3 }, { "key": "Esophagogastric Cancer", "value": 2 }, { "key": "Kidney Cancer, NOS", "value": 2 }, { "key": "Cervical Cancer, NOS", "value": 1 }, { "key": "Infiltrating Ductal Carcinoma", "value": 1 } ], "tissue_type": [ { "key": "Bowel", "value": 57 }, { "key": "Endometrioid endometrial adenocarcinoma", "value": 23 }, { "key": "Lung", "value": 11 }, { "key": "Pancreas", "value": 9 }, { "key": "Esophagus/Stomach", "value": 6 }, { "key": "CNS/Brain", "value": 3 }, { "key": "Kidney", "value": 2 }, { "key": "Cervix", "value": 1 }, { "key": "Infiltrating Ductal Carcinoma", "value": 1 } ] } ], "saphetor_known_pathogenicity": [ { "version": "25-Apr-2025", "items": [ { "annotations": { "NCBI ClinVar2": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "NCBI ClinVar2", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "submission_count": 34, "review_stars": 2, "accession_count": 21, "publication_count": 31, "clinical_significance": [ "likely pathogenic", "pathogenic" ], "pub_med_references": [ 26242988, 26521233, 29298116, 30443000, 30544177, 30902772, 30936194, 31836588, 31891627, 34114335, 35794233 ], "possible_functional_studies": [ "21079152", "29298116" ], "disease_name": [ "Acute Myeloid Leukemia", "Acute Myeloid Leukemia, Adult", "Aml Adult", "Aplasia Cutis Congenita Epibulbar Dermoids", "Arteriovenous Malformations of the Brain" ] } ], "Saphetor VarSome Comment": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2018-02-14 06:57:59", "id": 2138, "saphetorClass": "pathogenic", "user_id": 2582, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "ClinVar: Pathogenic", "flagged_at_timestamp": "2018-12-26 13:52:35", "id": 4746, "saphetorClass": "pathogenic", "user_id": 1299, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2019-02-05 11:23:49", "id": 5723, "saphetorClass": "pathogenic", "user_id": 3509, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2019-04-04 12:24:43", "id": 7452, "saphetorClass": "pathogenic", "user_id": 5939, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2019-07-31 12:34:46", "id": 11201, "saphetorClass": "pathogenic", "user_id": 2400, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2019-10-29 11:45:52", "id": 13722, "saphetorClass": "pathogenic", "user_id": 5387, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "", "flagged_at_timestamp": "2019-11-14 14:25:19", "id": 14368, "saphetorClass": "pathogenic", "user_id": 10790, "variant_id": 10190120253982840004 }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor VarSome Comment", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "comment": "AML FAB M2 with dysplastic features in a child; CD34+ très partiel, CD117+ partial, HLA-DR+, CD13+ et CD33+; CD123, du CD371+; 46,XX; FLT3 c.1777_1778ins45 ; p.(Val592_Asp593ins15) ; VAF=5%; TET2 c.4096C>T ; p.(Arg1366Cys) ; VAF=1% .", "flagged_at_timestamp": "2019-12-11 10:29:27", "id": 15104, "saphetorClass": "pathogenic", "user_id": 13087, "variant_id": 10190120253982840004 } ], "Saphetor PubMedUserEntry": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 39501138 ], "pathogenicity": "P", "id": 56484, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 37772552 ], "pathogenicity": "DR", "id": 47584, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 37010994 ], "pathogenicity": "DR", "id": 42987, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 36627374 ], "pathogenicity": "DR", "id": 41427, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 36523988 ], "pathogenicity": "P", "id": 41072, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 36414681 ], "pathogenicity": "P", "id": 40551, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 35907592 ], "pathogenicity": "DR", "id": 37806, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 35075146 ], "pathogenicity": "P", "id": 31450, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 33917572 ], "pathogenicity": "P", "id": 31449, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 28797274 ], "pathogenicity": "P", "id": 30616, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 21285991 ], "pathogenicity": "DA", "id": 29760, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22683711 ], "pathogenicity": "P", "id": 28808, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22683711 ], "pathogenicity": "P", "id": 28807, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 30368666 ], "pathogenicity": "DA", "id": 26734, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 23497191 ], "id": 23039, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22247021 ], "id": 23038, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22266220 ], "pathogenicity": "P", "id": 21585, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 33538228 ], "pathogenicity": "P", "id": 21274, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 31649840 ], "id": 20045, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 32903495 ], "id": 20044, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 23497191 ], "pathogenicity": "P", "id": 19252, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 31409810 ], "pathogenicity": "P", "id": 18693, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 27221540 ], "pathogenicity": "P", "id": 16643, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 29575536 ], "pathogenicity": "P", "id": 16638, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 27154293 ], "pathogenicity": "P", "id": 16625, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 32810914 ], "pathogenicity": "P", "id": 16408, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 24225759 ], "pathogenicity": "P", "id": 13851, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 29846100 ], "pathogenicity": "P", "id": 13804, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22407852 ], "pathogenicity": "P", "id": 9667, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 30891959 ], "pathogenicity": "P", "id": 5904, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 25553307 ], "id": 5534, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 19087308 ], "id": 5443, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 27123948 ], "pathogenicity": "P", "id": 3482, "confirmedByFunctionalStudy": false }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 23497191 ], "pathogenicity": "P", "id": 23039, "confirmedByFunctionalStudy": false, "is_lifted_over": true, "lifted_from": "chr12:25245350 C⇒T" }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 22247021 ], "pathogenicity": "P", "id": 23038, "confirmedByFunctionalStudy": false, "is_lifted_over": true, "lifted_from": "chr12:25245350 C⇒T" }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 31649840 ], "pathogenicity": "DA", "id": 20045, "confirmedByFunctionalStudy": false, "is_lifted_over": true, "lifted_from": "chr12:25245350 C⇒T" }, { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "pub_med_references": [ 32903495 ], "pathogenicity": "DA", "id": 20044, "confirmedByFunctionalStudy": false, "is_lifted_over": true, "lifted_from": "chr12:25245350 C⇒T" } ], "UNIPROT UniProt Variants": [ { "functions": [ "coding" ], "coding_impact": "missense", "acmg_confirmed": true, "acmg_class": "Pathogenic", "acmg_reannotated": "Pathogenic", "source": "UNIPROT UniProt Variants", "codon": 12, "gene_symbol": "KRAS", "hgvs": "G12D", "transcript": "NM_004985.5", "possible_functional_studies": [ 21079152, 29298116 ], "pub_med_references": [ 16533793, 17332249, 20805368, 20949522, 21079152, 22499344, 22683711, 29298116, 30891959, 34820593 ], "disease_name": [ "Acute myeloid leukemia", "Atypical endometrial hyperplasia", "Autoimmune lymphoproliferative syndrome type 4", "Capillary malformation-arteriovenous malformation 1", "Carcinoma of pancreas" ], "annotation_id": "VAR_016026" } ] } } ] } ], "acmg_annotation": { "version_name": "13.3.0", "gene_symbol": "KRAS", "transcript": "NM_004985.5", "transcript_reason": "MANE select", "coding_impact": "missense", "blosum_score": -4, "verdict": { "ACMG_rules": { "benign_score": 0, "benign_subscore": "Uncertain Significance", "clinical_score": 5.271, "pathogenic_score": 21, "pathogenic_subscore": "Pathogenic", "total_score": 21, "verdict": "Pathogenic" }, "classifications": [ "PS3_Very Strong", "PM1_Strong", "PM5_Strong", "PP3_Moderate", "PP5_Moderate", "PM2_Supporting" ] }, "classifications": [ { "name": "PS3", "met_criteria": true, "user_explain": [ "Combined evidence strength is Very Strong (score = 9). .", "Very Strong: ClinVar classifies this variant as Pathogenic, 2 stars (reviewed Feb '25, 34 submissions of which 3 are from high confidence submitters), backed by functional studies (requires user validation) mentioned in 2 articles (%%PUBMED:29298116%% and %%PUBMED:21079152%%), and also citing 10 articles (%%PUBMED:35794233%%, %%PUBMED:34114335%%, %%PUBMED:31891627%%, %%PUBMED:31836588%%, %%PUBMED:30936194%%, and 5 more), associated with Acute Myeloid Leukemia and Arteriovenous Malformations of the Brain.", "Supporting: UniProt Variants classifies this variant as Pathogenic, backed by functional studies (requires user validation) mentioned in 2 articles (%%PUBMED:29298116%% and %%PUBMED:21079152%%), and also citing 9 articles (%%PUBMED:34820593%%, %%PUBMED:30891959%%, %%PUBMED:22683711%%, %%PUBMED:22499344%%, %%PUBMED:20949522%%, and 4 more), associated with Acute myeloid leukemia, Atypical endometrial hyperplasia, Autoimmune lymphoproliferative syndrome type 4, and 2 more." ], "strength": "Very Strong" }, { "name": "PM1", "met_criteria": true, "user_explain": [ "Hot-spot of length 17 amino-acids has 51 missense/in-frame variants (30 pathogenic variants, 21 uncertain variants, and no benign), which qualifies as strong pathogenic.", "UniProt protein RASK_HUMAN binding site 'Other binding site_10-18' has 36 missense/in-frame variants (24 pathogenic variants, 12 uncertain variants, and no benign), which qualifies as moderate pathogenic." ], "strength": "Strong" }, { "name": "PM5", "met_criteria": true, "user_explain": [ "Alternative variant ##chr12:25398285 C⇒T## (Gly12Ser) is classified Pathogenic by UniProt Variants (confirmed using the germline classifier).", "Alternative variant ##chr12:25398285 C⇒G## (Gly12Arg) is classified Pathogenic by the VarSome community (confirmed using the germline classifier).", "Alternative variant ##chr12:25398285 C⇒A## (Gly12Cys) is classified Pathogenic by the VarSome community (confirmed using the germline classifier).", "Alternative variant ##chr12:25398284 C⇒G## (Gly12Ala) is classified Pathogenic by the VarSome community (confirmed using the germline classifier).", "Alternative variant ##chr12:25398284 C⇒A## (Gly12Val) is classified Pathogenic by UniProt Variants (confirmed using the germline classifier).", "Alternative variant ##chr12:25398284 CC⇒GA## (Gly12Ser) is classified Pathogenic by the VarSome community in article %%PUBMED:32308773%% (confirmed using the germline classifier).", "Alternative variant ##chr12:25398283 ACC⇒CCA## (Gly12Trp) is classified Pathogenic by the VarSome community in article %%PUBMED:33075161%% (confirmed using the germline classifier).", "7 pathogenic alternative variants identified." ], "strength": "Strong" }, { "name": "PP3", "met_criteria": true, "user_explain": [ "MetaRNN = 0.898 is between 0.841 and 0.939 ⇒ moderate pathogenic." ], "strength": "Moderate" }, { "name": "PP5", "met_criteria": true, "user_explain": [ "Moderate: the VarSome community has classified this variant as Pathogenic, citing 17 articles (%%PUBMED:35075146%%, %%PUBMED:33917572%%, %%PUBMED:33538228%%, %%PUBMED:32810914%%, %%PUBMED:31409810%%, and 12 more)." ], "strength": "Moderate" }, { "name": "PM2", "met_criteria": true, "user_explain": [ "Variant not found in gnomAD genomes, good gnomAD genomes coverage = 31.3.", "GnomAD exomes allele count = 1 is less than 5 for AD gene KRAS, good gnomAD exomes coverage = 59.5." ], "strength": "Supporting" } ], "gene_id": 12340, "sample_findings": { "phenotypes": "No matching phenotype found for gene KRAS which is associated with 609942, 615278, Acute Myeloid Leukemia, Arteriovenous Malformations of the Brain, and 34 more, according to CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp, and gene2phenotype.", "mode_of_inheritance": "AD, based on gene information from CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp, and gene2phenotype." } }, "amp_annotation": { "version_name": "13.3.0", "verdict": { "tier": "Tier II", "approx_score": 2.3449999999999993 }, "classifications": [ { "name": "Crtd", "tier": "Tier II", "user_explain": { "Tier II": [ "Bowel Cancer, Lung Cancer, Ovary/Fallopian Tube, and Pancreas Cancer, 3 therapies (Cetuximab, Dactolisib + Selumetinib, and Panitumumab), actionable, prognostic, and diagnostic, Clinical Evidence, pre-clinical, and case reports, from CIViC, citing %%PUBMED:27959684%%, %%PUBMED:27010960%%, %%PUBMED:23565280%%, %%PUBMED:23014527%%, and 5 more. No patient information was provided to match the cancer." ], "Tier III": [ "Bowel Cancer, Lung Cancer, Hairy Cell Leukemia, Melanoma, and 2 more, 8 therapies (Vemurafenib, Akt Inhibitor Mk2206, Cetuximab + Panitumumab, Dabrafenib, and 4 more), actionable, case reports, pre-clinical, and Clinical Evidence, from CIViC, citing %%PUBMED:26352686%%, %%PUBMED:26161928%%, %%PUBMED:24265155%%, %%PUBMED:23524406%%, and 8 more. No patient information was provided to match the cancer.", "Variant not found in CKB." ] }, "approx_score": 9.0 }, { "name": "Drug", "tier": "Tier II", "user_explain": { "Tier II": [ "3 therapies (Cetuximab, Dactolisib + Selumetinib, and Panitumumab), Actionable, Prognostic, and Diagnostic, Clinical Evidence, pre-clinical, and case reports, from CIViC. Citing %%PUBMED:27959684%%, %%PUBMED:27010960%%, %%PUBMED:23565280%%, %%PUBMED:23014527%%, and 5 more. Related to Bowel Cancer, Lung Cancer, Ovary/Fallopian Tube, and Pancreas Cancer. No patient information was provided to match the cancer." ], "Tier III": [ "Searches for drugs or clinical trials are disabled because there is Tier II curated drug evidence for this variant.", "8 therapies (Vemurafenib, Akt Inhibitor Mk2206, Cetuximab + Panitumumab, Dabrafenib, and 4 more), Actionable, case reports, pre-clinical, and Clinical Evidence, from CIViC. Citing %%PUBMED:26352686%%, %%PUBMED:26161928%%, %%PUBMED:24265155%%, %%PUBMED:23524406%%, and 8 more. Related to Bowel Cancer, Lung Cancer, Hairy Cell Leukemia, Melanoma, and 2 more. No patient information was provided to match the cancer." ] }, "approx_score": 8.0 }, { "name": "Germ", "tier": "Tier I", "user_explain": { "Tier I": [ "This missense variant is classified Pathogenic by the germline classifier, using rules PS3_Very Strong, PM1_Strong, PM5_Strong, PP3_Moderate, PP5_Moderate, and PM2_Supporting." ] }, "approx_score": 7.0 }, { "name": "Path", "tier": "Tier II", "user_explain": { "Tier II": [ "Consensus associates gene KRAS with the following 29 cancers: Acute Myeloid Leukemia, Bladder/Urinary Tract, Breast, Central carbon metabolism in cancer, Choline metabolism in cancer, and 24 more.", "GHR reports that the KRAS gene provides instructions for making a protein called K-Ras that is part of a signaling pathway known as the RAS/MAPK pathway. Also, associates KRAS with the following 5 cancers: Autoimmune Lymphoproliferative Syndrome, Cholangiocarcinoma, Lung, Myeloid, and Nevus, Epidermal.", "KEGG reports that gene KRAS is involved in B cell receptor signaling pathway, ErbB signaling pathway, Fc epsilon RI signaling pathway, GnRH signaling pathway, Insulin signaling pathway, and 3 more. Also, associates KRAS with the following 12 cancers: Acute Myeloid Leukemia, Bladder/Urinary Tract, Colorectal cancer, Endometrial cancer, Glioma, and 7 more.", "Mondo associates gene KRAS with the following 14 cancers: Acute Myeloid Leukemia, Arteriovenous Malformations of the Brain, Autoimmune Lymphoproliferative Syndrome Type 4, Differentiated Thyroid Carcinoma, Encephalocraniocutaneous Lipomatosis, and 9 more.", "The Human Protein Atlas classifies KRAS as an oncogene." ] }, "approx_score": 6.0 }, { "name": "Pubs", "tier": "Tier I", "user_explain": { "Tier I": [ "VarSome users have linked 21 articles stating the variant is pathogenic (%%PUBMED:39501138%%, %%PUBMED:36523988%%, %%PUBMED:36414681%%, %%PUBMED:35075146%%, %%PUBMED:33917572%%, and 16 more) (3 by VarSome curation team)(4 entries have been automatically lifted over from hg38)." ] }, "approx_score": 5.0 }, { "name": "Soma", "tier": "Tier I", "user_explain": { "Tier I": [ "This variant is reported in 5 967 out of the 18 372 somatic samples for gene KRAS, which has 802 reported somatic variants. Its GnomAD ƒ = 0.00000401. This is statistically rated Tier I." ], "Tier III": [ "CBioPortal reports 5 006 samples, cancer type = 1 373 x Pancreatic Cancer, 1 250 x Colorectal Cancer, 717 x Non-Small Cell Lung Cancer, and 46 more, sample type = 2 816 x Primary, 1 253 x Metastasis, 29 x Primary Tumor, and 6 more, tissue = 1 690 x Bowel, 1 546 x Pancreas, 723 x Lung, and 26 more, citing 55 articles (%%PUBMED:30463544%%, %%PUBMED:29721857%%, %%PUBMED:29525983%%, %%PUBMED:29298116%%, %%PUBMED:27872090%%, and 50 more).", "CancerHotspots reports 758 samples, bio-type = 1 x protein_coding, cancer type = 324 x Pancreatic Cancer, 178 x Colorectal Cancer, 85 x Non-Small Cell Lung Cancer, and 25 more, tissue site = 324 x Pancreas, 213 x Bowel, 86 x Lung, and 22 more.", "GDC reports 203 samples, drugs = 18 x Oxaliplatin, 13 x Fluorouracil, 10 x Leucovorin, and 34 more, outcomes = 65 x Disease Free and 38 x Recurred, sex = 61 x Female and 53 x Male, tissues = 57 x Bowel, 23 x Endometrioid endometrial adenocarcinoma, 11 x Lung, and 6 more.", "Variant not found in ICGC." ] }, "total_samples": 5967, "approx_score": 4.0 }, { "name": "Freq", "tier": "Tier II", "user_explain": { "Tier II": [ "Variant not found in gnomAD genomes, good gnomAD genomes coverage = 31.3.\nGnomAD exomes allele count = 1 is less than 5 for AD gene KRAS, good gnomAD exomes coverage = 59.5." ] }, "approx_score": 3.0 }, { "name": "Type", "tier": "Tier III", "user_explain": { "Tier III": [ "No relevant information.", "Variant is not predicted splicing: no prediction from MaxEntScan." ] }, "approx_score": 2.0 }, { "name": "Pred", "tier": "Tier II", "user_explain": { "Tier II": [ "Moderate pathogenic in-silico prediction: MetaRNN = 0.898 is between 0.841 and 0.939 ⇒ moderate pathogenic." ] }, "approx_score": 1.0 } ] }, "cbio_portal": [ { "version": "06-Jun-2023", "total_samples": 5006, "sample_id": null, "sample_type": [ { "key": "Primary", "value": 2816 }, { "key": "Metastasis", "value": 1253 }, { "key": "Primary Tumor", "value": 29 }, { "key": "Metastatic", "value": 26 }, { "key": "Recurrent", "value": 4 }, { "key": "Local Recurrence", "value": 3 }, { "key": "Met", "value": 2 }, { "key": "Cell Line", "value": 1 }, { "key": "Recurrence", "value": 1 } ], "study_name": null, "mutation_status": [ { "key": "Somatic", "value": 3019 }, { "key": "Somatic_Vs_Pool", "value": 1 } ], "validation_status": [ { "key": "Valid", "value": 190 }, { "key": "Untested", "value": 63 }, { "key": "High", "value": 33 }, { "key": "Not_Done", "value": 9 }, { "key": "Validated", "value": 9 }, { "key": "__Unknown__,Valid,Valid", "value": 1 } ], "center": [ { "key": "Mskcc", "value": 2502 }, { "key": "Broad.Mit.Edu", "value": 211 }, { "key": "Qcmg.Uq.Edu.Au", "value": 160 }, { "key": "Genome.Wustl.Edu", "value": 70 }, { "key": "Dfci.Harvard.Edu", "value": 45 }, { "key": "Hgsc.Bcm.Edu", "value": 41 }, { "key": "Ut Southwestern", "value": 37 }, { "key": "Baylor College Of Medicine", "value": 29 }, { "key": "Papaemmanuil_Nejm_2016", "value": 19 }, { "key": "Mskcc-Cmo", "value": 17 }, { "key": "Target", "value": 12 }, { "key": "Msk-Impact468", "value": 10 }, { "key": "Msk-Impact410", "value": 10 }, { "key": "Genentech", "value": 9 }, { "key": "Ohsu.Edu", "value": 9 }, { "key": "University Of Michigan", "value": 8 }, { "key": "Http://Www.Wuxiapptec.Com", "value": 7 }, { "key": "Oicr.On.Ca", "value": 7 }, { "key": "Mskcc.Org", "value": 7 }, { "key": "Omrf.Org", "value": 6 }, { "key": "Msk-Impact410+Idtcustom_18_20161108", "value": 6 }, { "key": "Msk-Impact410+Kinghamt20150127Spikein", "value": 4 }, { "key": "Foundation", "value": 4 }, { "key": "Msk-Impact341+Kinghamt20150127Spikein", "value": 3 }, { "key": "Msk-Impact", "value": 3 }, { "key": "Papaemmanuil_Mds_2013", "value": 3 }, { "key": "John Hopkins", "value": 3 }, { "key": "Metabric", "value": 2 }, { "key": "Nccs", "value": 2 }, { "key": "Mdanderson.Org/Ucsc.Edu/Broad.Mit.Edu", "value": 2 }, { "key": "Wcm", "value": 2 }, { "key": "Pfizer_Uhongkong", "value": 2 }, { "key": "St. Jude Children'S Research Hospital", "value": 2 }, { "key": "Www.Unioviedo.Es/Iuopa/", "value": 1 }, { "key": "Discover.Nci.Nih.Gov", "value": 1 }, { "key": "Uhongkong", "value": 1 }, { "key": "Tokyo", "value": 1 }, { "key": "Genome.Wustl.Edu;Unc.Edu", "value": 1 }, { "key": "Jhu", "value": 1 }, { "key": "Laml-Kr", "value": 1 }, { "key": "Laml-Us", "value": 1 }, { "key": "Msk-Impact341", "value": 1 } ], "t_ref_count": 1828155, "t_alt_count": 542591, "n_ref_count": 1349588, "n_alt_count": 1562, "n_depth": 64933, "t_depth": 86627, "canonical": true, "hotspot": false, "ensp": "ENSP00000256078", "ccds": "CCDS8703.1", "cdsposition": "35/570", "cdnaposition": "99/1119", "biotype": "Protein_Coding", "uniparc": "UPI0000133132", "pick": 1.0, "sex": [ { "key": "Female", "value": 2418 }, { "key": "Male", "value": 2306 } ], "age_freq": [ { "key": "60-70", "value": 386 }, { "key": "70-80", "value": 283 }, { "key": "50-60", "value": 206 }, { "key": "40-50", "value": 104 }, { "key": "80-90", "value": 87 }, { "key": "30-40", "value": 35 }, { "key": "10-20", "value": 9 }, { "key": "90-100", "value": 8 }, { "key": "20-30", "value": 7 }, { "key": "1-5", "value": 5 }, { "key": "5-10", "value": 5 }, { "key": "<1", "value": 3 } ], "os_months": [ { "key": "0", "value": 145 }, { "key": "13", "value": 113 }, { "key": "4", "value": 109 }, { "key": "15", "value": 108 }, { "key": "14", "value": 108 }, { "key": "1", "value": 107 }, { "key": "7", "value": 102 }, { "key": "10", "value": 101 }, { "key": "11", "value": 101 }, { "key": "5", "value": 100 }, { "key": "9", "value": 97 }, { "key": "6", "value": 97 }, { "key": "2", "value": 96 }, { "key": "18", "value": 95 }, { "key": "12", "value": 94 }, { "key": "8", "value": 89 }, { "key": "3", "value": 86 }, { "key": "17", "value": 80 }, { "key": "16", "value": 75 }, { "key": "20", "value": 60 }, { "key": "23", "value": 59 }, { "key": "24", "value": 58 }, { "key": "21", "value": 57 }, { "key": "19", "value": 56 }, { "key": "25", "value": 47 }, { "key": "22", "value": 46 }, { "key": "26", "value": 44 }, { "key": "31", "value": 41 }, { "key": "27", "value": 40 }, { "key": "29", "value": 37 }, { "key": "28", "value": 36 }, { "key": "33", "value": 36 }, { "key": "37", "value": 34 }, { "key": "36", "value": 34 }, { "key": "32", "value": 30 }, { "key": "30", "value": 28 }, { "key": "35", "value": 27 }, { "key": "44", "value": 24 }, { "key": "45", "value": 22 }, { "key": "43", "value": 21 }, { "key": "47", "value": 20 }, { "key": "41", "value": 19 }, { "key": "51", "value": 18 }, { "key": "42", "value": 17 }, { "key": "50", "value": 17 }, { "key": "48", "value": 17 }, { "key": "34", "value": 16 }, { "key": "39", "value": 15 }, { "key": "46", "value": 15 }, { "key": "52", "value": 14 }, { "key": "60", "value": 14 }, { "key": "49", "value": 13 }, { "key": "38", "value": 13 }, { "key": "59", "value": 12 }, { "key": "64", "value": 11 }, { "key": "57", "value": 11 }, { "key": "62", "value": 10 }, { "key": "55", "value": 10 }, { "key": "56", "value": 9 }, { "key": "61", "value": 9 }, { "key": "53", "value": 8 }, { "key": "86", "value": 7 }, { "key": "40", "value": 7 }, { "key": "58", "value": 7 }, { "key": "65", "value": 7 }, { "key": "72", "value": 7 }, { "key": "79", "value": 6 }, { "key": "67", "value": 6 }, { "key": "66", "value": 5 }, { "key": "54", "value": 4 }, { "key": "118", "value": 4 }, { "key": "63", "value": 4 }, { "key": "100", "value": 4 }, { "key": "68", "value": 4 }, { "key": "74", "value": 3 }, { "key": "77", "value": 3 }, { "key": "71", "value": 3 }, { "key": "75", "value": 3 }, { "key": "97", "value": 3 }, { "key": "117", "value": 2 }, { "key": "70", "value": 2 }, { "key": "92", "value": 2 }, { "key": "165", "value": 2 }, { "key": "89", "value": 2 }, { "key": "145", "value": 2 }, { "key": "85", "value": 2 }, { "key": "84", "value": 2 }, { "key": "124", "value": 2 }, { "key": "120", "value": 2 }, { "key": "111", "value": 2 }, { "key": "88", "value": 1 }, { "key": "80", "value": 1 }, { "key": "101", "value": 1 }, { "key": "93", "value": 1 }, { "key": "76", "value": 1 }, { "key": "95", "value": 1 }, { "key": "182", "value": 1 }, { "key": "98", "value": 1 }, { "key": "147", "value": 1 }, { "key": "183", "value": 1 }, { "key": "172", "value": 1 }, { "key": "170", "value": 1 }, { "key": "167", "value": 1 }, { "key": "202", "value": 1 }, { "key": "152", "value": 1 }, { "key": "150", "value": 1 }, { "key": "148", "value": 1 }, { "key": "73", "value": 1 }, { "key": "139", "value": 1 }, { "key": "138", "value": 1 }, { "key": "137", "value": 1 }, { "key": "122", "value": 1 }, { "key": "113", "value": 1 }, { "key": "109", "value": 1 }, { "key": "103", "value": 1 } ], "os_status": [ { "key": "Deceased", "value": 1875 }, { "key": "Living", "value": 1626 }, { "key": "No", "value": 9 }, { "key": " ", "value": 4 }, { "key": "Yes", "value": 4 }, { "key": "Doc", "value": 1 }, { "key": "Ltf", "value": 1 } ], "race": [ { "key": "European (non-Finnish)", "value": 2101 }, { "key": "African", "value": 195 }, { "key": "Latino", "value": 80 }, { "key": "Other", "value": 48 }, { "key": "East Asian", "value": 3 } ], "tumor_status": [ { "key": "Disease Free", "value": 186 }, { "key": "Recurred", "value": 80 } ], "dfs_months": [ { "key": "4", "value": 20 }, { "key": "2", "value": 13 }, { "key": "16", "value": 12 }, { "key": "13", "value": 12 }, { "key": "3", "value": 11 }, { "key": "15", "value": 9 }, { "key": "23", "value": 8 }, { "key": "14", "value": 8 }, { "key": "7", "value": 8 }, { "key": "10", "value": 8 }, { "key": "1", "value": 7 }, { "key": "5", "value": 6 }, { "key": "9", "value": 6 }, { "key": "37", "value": 6 }, { "key": "32", "value": 6 }, { "key": "27", "value": 6 }, { "key": "36", "value": 6 }, { "key": "12", "value": 6 }, { "key": "33", "value": 5 }, { "key": "47", "value": 5 }, { "key": "6", "value": 5 }, { "key": "24", "value": 5 }, { "key": "22", "value": 4 }, { "key": "49", "value": 4 }, { "key": "0", "value": 4 }, { "key": "35", "value": 4 }, { "key": "118", "value": 3 }, { "key": "60", "value": 3 }, { "key": "45", "value": 3 }, { "key": "41", "value": 3 }, { "key": "8", "value": 3 }, { "key": "50", "value": 3 }, { "key": "31", "value": 3 }, { "key": "86", "value": 3 }, { "key": "19", "value": 3 }, { "key": "79", "value": 3 }, { "key": "52", "value": 2 }, { "key": "64", "value": 2 }, { "key": "53", "value": 2 }, { "key": "72", "value": 2 }, { "key": "58", "value": 2 }, { "key": "43", "value": 2 }, { "key": "42", "value": 2 }, { "key": "38", "value": 2 }, { "key": "17", "value": 2 }, { "key": "34", "value": 2 }, { "key": "11", "value": 2 }, { "key": "20", "value": 2 }, { "key": "26", "value": 2 }, { "key": "97", "value": 2 }, { "key": "85", "value": 1 }, { "key": "88", "value": 1 }, { "key": "95", "value": 1 }, { "key": "48", "value": 1 }, { "key": "62", "value": 1 }, { "key": "61", "value": 1 }, { "key": "57", "value": 1 }, { "key": "54", "value": 1 }, { "key": "148", "value": 1 }, { "key": "18", "value": 1 }, { "key": "30", "value": 1 }, { "key": "29", "value": 1 }, { "key": "28", "value": 1 }, { "key": "25", "value": 1 }, { "key": "21", "value": 1 } ], "path_t_stage": [ { "key": "T3", "value": 106 }, { "key": "T2", "value": 30 }, { "key": "pT3", "value": 24 }, { "key": "T4", "value": 16 }, { "key": "T1", "value": 10 }, { "key": "T4A", "value": 8 }, { "key": "T1B", "value": 5 }, { "key": "T3B", "value": 4 }, { "key": "Tx", "value": 3 }, { "key": "T4B", "value": 3 }, { "key": "T1A", "value": 3 }, { "key": "T2A", "value": 2 }, { "key": "T2B", "value": 2 }, { "key": "T1b", "value": 2 }, { "key": "T1B1", "value": 2 }, { "key": "T4a", "value": 2 }, { "key": "pT2", "value": 1 }, { "key": "pT4", "value": 1 }, { "key": "pT1", "value": 1 }, { "key": "pTa", "value": 1 }, { "key": "T3A", "value": 1 }, { "key": "T4b", "value": 1 }, { "key": "T3b", "value": 1 }, { "key": "<T2", "value": 1 }, { "key": "T2A2", "value": 1 }, { "key": "T1C", "value": 1 }, { "key": ">=T2", "value": 1 } ], "pfs_status": [ { "key": "Yes", "value": 191 }, { "key": "No", "value": 156 } ], "radiation_therapy": [ { "key": "No", "value": 160 }, { "key": "Yes", "value": 51 } ], "path_n_stage": [ { "key": "N0", "value": 86 }, { "key": "N1", "value": 65 }, { "key": "N2", "value": 14 }, { "key": "NX", "value": 7 }, { "key": "N1B", "value": 6 }, { "key": "N2B", "value": 3 }, { "key": "N1A", "value": 2 }, { "key": "N1C", "value": 1 }, { "key": "N2A", "value": 1 } ], "path_m_stage": [ { "key": "M0", "value": 111 }, { "key": "MX", "value": 58 }, { "key": "M1", "value": 8 }, { "key": "M1A", "value": 3 }, { "key": "M1B", "value": 1 } ], "new_tumor_event_after_initial_treatment": [ { "key": "No", "value": 118 }, { "key": "NO", "value": 56 }, { "key": "Yes", "value": 56 }, { "key": "YES", "value": 31 } ], "ajcc_pathologic_tumor_stage": [ { "key": "IIB", "value": 95 }, { "key": "Stage IIB", "value": 48 }, { "key": "STAGE IIB", "value": 41 }, { "key": "STAGE IIA", "value": 23 }, { "key": "IIA", "value": 19 }, { "key": "Stage IIA", "value": 17 }, { "key": "STAGE IV", "value": 15 }, { "key": "STAGE I", "value": 15 }, { "key": "STAGE II", "value": 13 }, { "key": "Stage I", "value": 12 }, { "key": "Stage II", "value": 9 }, { "key": "STAGE IIIB", "value": 9 }, { "key": "STAGE III", "value": 9 }, { "key": "STAGE IB", "value": 9 }, { "key": "STAGE IA", "value": 8 }, { "key": "Stage IV", "value": 8 }, { "key": "IV", "value": 7 }, { "key": "IB", "value": 7 }, { "key": "Stage IIIC", "value": 6 }, { "key": "STAGE IIIC", "value": 6 }, { "key": "Stage IB", "value": 6 }, { "key": "STAGE IIIA", "value": 6 }, { "key": "STAGE IVA", "value": 5 }, { "key": "Stage III", "value": 5 }, { "key": "Stage IA", "value": 3 }, { "key": "Stage IIIA", "value": 3 }, { "key": "Stage IIIB", "value": 3 }, { "key": "III", "value": 3 }, { "key": "IA", "value": 2 }, { "key": "Stage IVA", "value": 1 } ], "dss_status": [ { "key": "0:Alive Or Dead Tumor Free", "value": 142 }, { "key": "1:Dead With Tumor", "value": 47 }, { "key": "0", "value": 41 }, { "key": "0:Alive", "value": 20 }, { "key": "1:Dead", "value": 8 }, { "key": "1", "value": 7 }, { "key": "1:Dead Of Melanoma", "value": 1 } ], "prior_dx": [ { "key": "No", "value": 185 }, { "key": "Yes", "value": 16 }, { "key": "Yes, History Of Synchronous And Or Bilateral Malignancy", "value": 1 } ], "somatic_status_freq": [ { "key": "Yes", "value": 2117 } ], "grade": [ { "key": "G2", "value": 58 }, { "key": "G3", "value": 49 }, { "key": "G1", "value": 15 }, { "key": "Mod Diff", "value": 15 }, { "key": "Poor Diff", "value": 12 }, { "key": "High Grade", "value": 11 }, { "key": "Grade 2", "value": 7 }, { "key": "GX", "value": 5 }, { "key": "Grade 1", "value": 5 }, { "key": "Grade 3", "value": 4 }, { "key": "HG", "value": 2 }, { "key": "Low Grade", "value": 2 }, { "key": "G4", "value": 2 }, { "key": "Intermediate Grade", "value": 1 }, { "key": "High", "value": 1 }, { "key": "Poorly", "value": 1 }, { "key": "Well Diff", "value": 1 } ], "pub_med_references": [ 2278970, 3122217, 7773929, 8439212, 12460918, 15696205, 15842656, 16361624, 16434492, 16618717, 17332249, 17384584, 17704260, 17910045, 18316791, 18794081, 19018267, 19029981, 19047918, 19075190, 19114683, 19255327, 19358724, 19679400, 19773371, 19794967, 19881948, 20609353, 20805368, 20921462, 20921465, 20949522, 21079152, 21169357, 21228335, 21398618, 21975775, 22025163, 22235099, 22282465, 22407852, 22499344, 22683711, 22897852, 23014527, 23182985, 23406027, 25044103, 25157968, 26372703, 27872090, 29298116, 29525983, 29721857, 30463544 ], "oncotree_code": [ { "key": "PAAD", "value": 1358 }, { "key": "LUAD", "value": 643 }, { "key": "COAD", "value": 633 }, { "key": "COADREAD", "value": 344 }, { "key": "READ", "value": 244 }, { "key": "BOWEL", "value": 215 }, { "key": "PANCREAS", "value": 173 }, { "key": "UEC", "value": 151 }, { "key": "MAAP", "value": 134 }, { "key": "IHCH", "value": 113 }, { "key": "EHCH", "value": 71 }, { "key": "BLCA", "value": 66 }, { "key": "STAD", "value": 56 }, { "key": "NSCLC", "value": 55 }, { "key": "AML", "value": 54 }, { "key": "CHOL", "value": 49 }, { "key": "APAD", "value": 31 }, { "key": "AMPCA", "value": 31 }, { "key": "MACR", "value": 28 }, { "key": "LGSOC", "value": 26 }, { "key": "SBC", "value": 26 }, { "key": "CUP", "value": 17 }, { "key": "ESCA", "value": 16 }, { "key": "GEJ", "value": 15 }, { "key": "UTUC", "value": 14 }, { "key": "UCEC", "value": 13 }, { "key": "IDC", "value": 13 }, { "key": "BLL", "value": 12 }, { "key": "UCS", "value": 11 }, { "key": "CTAAP", "value": 11 }, { "key": "GBC", "value": 10 }, { "key": "MIXED", "value": 9 }, { "key": "STOMACH", "value": 8 }, { "key": "GBM", "value": 8 }, { "key": "LUNE", "value": 8 }, { "key": "HGNEC", "value": 8 }, { "key": "ECAD", "value": 8 }, { "key": "PRCC", "value": 8 }, { "key": "AMLCBFBMYH11", "value": 8 }, { "key": "OVARY", "value": 8 }, { "key": "DA", "value": 7 }, { "key": "SKCM", "value": 7 }, { "key": "SEM", "value": 7 }, { "key": "PRAD", "value": 6 }, { "key": "USC", "value": 6 }, { "key": "GBAD", "value": 6 }, { "key": "SCLC", "value": 6 }, { "key": "ESCC", "value": 5 }, { "key": "OCSC", "value": 5 }, { "key": "PCM", "value": 5 }, { "key": "IPMN", "value": 5 }, { "key": "MOV", "value": 5 }, { "key": "PAASC", "value": 4 }, { "key": "HCC", "value": 4 }, { "key": "LUSC", "value": 4 }, { "key": "CCOV", "value": 4 }, { "key": "GCCAP", "value": 4 }, { "key": "MDS", "value": 4 }, { "key": "MEL", "value": 3 }, { "key": "PANET", "value": 3 }, { "key": "LUAS", "value": 3 }, { "key": "LXSC", "value": 3 }, { "key": "MGCT", "value": 3 }, { "key": "PSTAD", "value": 3 }, { "key": "ACYC", "value": 3 }, { "key": "LIVER", "value": 3 }, { "key": "MCN", "value": 3 }, { "key": "AMLNOS", "value": 3 }, { "key": "ISTAD", "value": 3 }, { "key": "TSTAD", "value": 3 }, { "key": "HGSOC", "value": 3 }, { "key": "PAMPCA", "value": 3 }, { "key": "MUP", "value": 3 }, { "key": "BRCA", "value": 3 }, { "key": "SOFT_TISSUE", "value": 3 }, { "key": "MNM", "value": 2 }, { "key": "MSTAD", "value": 2 }, { "key": "SCB", "value": 2 }, { "key": "ACRM", "value": 2 }, { "key": "NSGCT", "value": 2 }, { "key": "OCS", "value": 2 }, { "key": "THYC", "value": 2 }, { "key": "ADNOS", "value": 2 }, { "key": "AASTR", "value": 2 }, { "key": "AMLMRC", "value": 2 }, { "key": "USTAD", "value": 2 }, { "key": "BLAD", "value": 2 }, { "key": "BMGCT", "value": 2 }, { "key": "URCC", "value": 2 }, { "key": "UMEC", "value": 2 }, { "key": "CEAD", "value": 2 }, { "key": "CLLSLL", "value": 2 }, { "key": "CMML", "value": 2 }, { "key": "CSCC", "value": 2 }, { "key": "CUPNOS", "value": 2 }, { "key": "DSTAD", "value": 2 }, { "key": "THYM", "value": 2 }, { "key": "TMN", "value": 2 }, { "key": "UAD", "value": 2 }, { "key": "HGGNOS", "value": 2 }, { "key": "GINET", "value": 2 }, { "key": "EGC", "value": 2 }, { "key": "DIFG", "value": 2 }, { "key": "UCU", "value": 1 }, { "key": "SSRCC", "value": 1 }, { "key": "UCCC", "value": 1 }, { "key": "SRCCR", "value": 1 }, { "key": "USARC", "value": 1 }, { "key": "TMDS", "value": 1 }, { "key": "SBOV", "value": 1 }, { "key": "VYST", "value": 1 }, { "key": "TLL", "value": 1 }, { "key": "THPA", "value": 1 }, { "key": "WT", "value": 1 }, { "key": "SARCNOS", "value": 1 }, { "key": "CCBOV", "value": 1 }, { "key": "IMT", "value": 1 }, { "key": "ILC", "value": 1 }, { "key": "ICPN", "value": 1 }, { "key": "GNG", "value": 1 }, { "key": "GCTSTM", "value": 1 }, { "key": "ES", "value": 1 }, { "key": "CESC", "value": 1 }, { "key": "CERVIX", "value": 1 }, { "key": "KIDNEY", "value": 1 }, { "key": "BRCANOS", "value": 1 }, { "key": "BONE", "value": 1 }, { "key": "BCC", "value": 1 }, { "key": "AWDNET", "value": 1 }, { "key": "AODG", "value": 1 }, { "key": "ANSC", "value": 1 }, { "key": "ALL", "value": 1 }, { "key": "RMS", "value": 1 }, { "key": "LCLC", "value": 1 }, { "key": "LIHB", "value": 1 }, { "key": "LUACC", "value": 1 }, { "key": "LUPC", "value": 1 }, { "key": "MPN", "value": 1 }, { "key": "MXOV", "value": 1 }, { "key": "NBL", "value": 1 }, { "key": "NECNOS", "value": 1 }, { "key": "NSCLCPD", "value": 1 }, { "key": "ODG", "value": 1 }, { "key": "OHNCA", "value": 1 }, { "key": "OPHSC", "value": 1 }, { "key": "OVT", "value": 1 }, { "key": "PDC", "value": 1 }, { "key": "PHCH", "value": 1 } ], "cancer_name": [ { "key": "Pancreatic Cancer", "value": 1543 }, { "key": "Colorectal Cancer", "value": 1221 }, { "key": "Non-Small Cell Lung Cancer", "value": 676 }, { "key": "Colorectal Carcinoma", "value": 215 }, { "key": "Appendiceal Cancer", "value": 180 }, { "key": "Endometrial Cancer", "value": 175 }, { "key": "Esophagogastric Cancer", "value": 110 }, { "key": "Hepatobiliary Cancer", "value": 105 }, { "key": "Bladder Cancer", "value": 84 }, { "key": "Intrahepatic Cholangiocarcinoma", "value": 76 }, { "key": "Leukemia", "value": 58 }, { "key": "Ovarian Cancer", "value": 43 }, { "key": "Extrahepatic Cholangiocarcinoma", "value": 42 }, { "key": "Non Small Cell Lung Cancer", "value": 37 }, { "key": "Cancer of Unknown Primary", "value": 32 }, { "key": "Ampullary Cancer", "value": 31 }, { "key": "Small Bowel Cancer", "value": 23 }, { "key": "Germ Cell Tumor", "value": 17 }, { "key": "Breast Cancer", "value": 16 }, { "key": "Glioma", "value": 15 }, { "key": "Melanoma", "value": 15 }, { "key": "Acute Myeloid Leukemia", "value": 15 }, { "key": "Gastrointestinal Neuroendocrine Tumor", "value": 14 }, { "key": "Cervical Cancer", "value": 11 }, { "key": "B-Lymphoblastic Leukemia/Lymphoma", "value": 10 }, { "key": "Small Bowel Carcinoma", "value": 10 }, { "key": "Head and Neck Cancer", "value": 9 }, { "key": "Gastric Cancer", "value": 8 }, { "key": "Ovarian Carcinoma", "value": 8 }, { "key": "Mature B-Cell Neoplasms", "value": 7 }, { "key": "Renal Cell Carcinoma", "value": 7 }, { "key": "Small Cell Lung Cancer", "value": 6 }, { "key": "Soft Tissue Sarcoma", "value": 6 }, { "key": "Gallbladder Carcinoma", "value": 6 }, { "key": "Endometrial Carcinoma", "value": 6 }, { "key": "Prostate Cancer", "value": 6 }, { "key": "Adenocarcinoma of Gallbladder", "value": 5 }, { "key": "Myelodysplastic Syndromes", "value": 4 }, { "key": "Liver Hepatocellular Carcinoma", "value": 3 }, { "key": "Salivary Cancer", "value": 3 }, { "key": "Renal Non-Clear Cell Carcinoma", "value": 3 }, { "key": "Intraductal Papillary Mucinous Neoplasm", "value": 3 }, { "key": "Thymic Tumor", "value": 3 }, { "key": "Ampullary Carcinoma", "value": 3 }, { "key": "Uterine Corpus Endometrial Carcinoma", "value": 3 }, { "key": "Lung cancer", "value": 2 }, { "key": "Skin Cancer, Non-Melanoma", "value": 2 }, { "key": "Bone Cancer", "value": 2 }, { "key": "Glioblastoma", "value": 2 }, { "key": "Myelodysplastic/Myeloproliferative Neoplasms", "value": 2 }, { "key": "Thyroid Cancer", "value": 1 }, { "key": "Uterine Sarcoma", "value": 1 }, { "key": "Wilms Tumor", "value": 1 }, { "key": "Thymic Epithelial Tumor", "value": 1 }, { "key": "T-Lymphoblastic Leukemia/Lymphoma", "value": 1 }, { "key": "Peripheral Nervous System", "value": 1 }, { "key": "Myeloproliferative Neoplasms", "value": 1 }, { "key": "Lung Cancer", "value": 1 }, { "key": "Lung Adenocarcinoma", "value": 1 }, { "key": "Kidney Renal Cell Carcinoma", "value": 1 }, { "key": "Invasive Breast Carcinoma", "value": 1 }, { "key": "Head and Neck Carcinoma", "value": 1 }, { "key": "Carcinoma of Uterine Cervix", "value": 1 }, { "key": "Blood Cancer, NOS", "value": 1 }, { "key": "Blood Cancer", "value": 1 }, { "key": "Anal Cancer", "value": 1 } ], "cancer_type": [ { "key": "Pancreatic Cancer", "value": 1373 }, { "key": "Colorectal Cancer", "value": 1250 }, { "key": "Non-Small Cell Lung Cancer", "value": 717 }, { "key": "Hepatobiliary Cancer", "value": 256 }, { "key": "Bowel Cancer, NOS", "value": 215 }, { "key": "Endometrial Cancer", "value": 184 }, { "key": "Appendiceal Cancer", "value": 180 }, { "key": "Pancreatic Cancer, NOS", "value": 173 }, { "key": "Esophagogastric Cancer", "value": 110 }, { "key": "Bladder Cancer", "value": 87 }, { "key": "Leukemia", "value": 70 }, { "key": "Ovarian Cancer", "value": 44 }, { "key": "Ampullary Cancer", "value": 34 }, { "key": "Small Bowel Cancer", "value": 33 }, { "key": "Cancer of Unknown Primary", "value": 32 }, { "key": "Breast Cancer", "value": 18 }, { "key": "Germ Cell Tumor", "value": 17 }, { "key": "Glioma", "value": 17 }, { "key": "Melanoma", "value": 15 }, { "key": "Gastrointestinal Neuroendocrine Tumor", "value": 14 }, { "key": "B-Lymphoblastic Leukemia/Lymphoma", "value": 12 }, { "key": "Cervical Cancer", "value": 11 }, { "key": "Head and Neck Cancer", "value": 10 }, { "key": "Renal Cell Carcinoma", "value": 10 }, { "key": "Esophageal/Stomach Cancer, NOS", "value": 8 }, { "key": "Ovarian/Fallopian Tube Cancer, NOS", "value": 8 }, { "key": "Mature B-Cell Neoplasms", "value": 7 }, { "key": "Small Cell Lung Cancer", "value": 6 }, { "key": "Prostate Cancer", "value": 6 }, { "key": "Myelodysplastic Syndromes", "value": 4 }, { "key": "Thymic Tumor", "value": 4 }, { "key": "Soft Tissue Sarcoma", "value": 3 }, { "key": "Soft Tissue Cancer, NOS", "value": 3 }, { "key": "Liver Cancer, NOS", "value": 3 }, { "key": "Salivary Gland Cancer", "value": 3 }, { "key": "Skin Cancer, Non-Melanoma", "value": 3 }, { "key": "Blood Cancer, NOS", "value": 2 }, { "key": "Myelodysplastic/Myeloproliferative Neoplasms", "value": 2 }, { "key": "T-Lymphoblastic Leukemia/Lymphoma", "value": 2 }, { "key": "Uterine Sarcoma", "value": 1 }, { "key": "Wilms Tumor", "value": 1 }, { "key": "Thyroid Cancer", "value": 1 }, { "key": "Peripheral Nervous System", "value": 1 }, { "key": "Myeloproliferative Neoplasms", "value": 1 }, { "key": "Kidney Cancer, NOS", "value": 1 }, { "key": "Cervical Cancer, NOS", "value": 1 }, { "key": "Bone Cancer, NOS", "value": 1 }, { "key": "Bone Cancer", "value": 1 }, { "key": "Anal Cancer", "value": 1 } ], "tissue_type": [ { "key": "Bowel", "value": 1690 }, { "key": "Pancreas", "value": 1546 }, { "key": "Lung", "value": 723 }, { "key": "Biliary Tract", "value": 251 }, { "key": "Uterus", "value": 185 }, { "key": "Esophagus/Stomach", "value": 118 }, { "key": "Bladder/Urinary Tract", "value": 87 }, { "key": "Myeloid", "value": 79 }, { "key": "Ovary/Fallopian Tube", "value": 52 }, { "key": "Ampulla of Vater", "value": 34 }, { "key": "Other", "value": 32 }, { "key": "Lymphoid", "value": 20 }, { "key": "CNS/Brain", "value": 19 }, { "key": "Breast", "value": 18 }, { "key": "Skin", "value": 18 }, { "key": "Head and Neck", "value": 13 }, { "key": "Testis", "value": 13 }, { "key": "Kidney", "value": 12 }, { "key": "Cervix", "value": 12 }, { "key": "Liver", "value": 8 }, { "key": "Prostate", "value": 6 }, { "key": "Soft Tissue", "value": 6 }, { "key": "Thymus", "value": 4 }, { "key": "Gastrointestinal Neuroendocrine Tumor", "value": 3 }, { "key": "Bone", "value": 2 }, { "key": "Germ Cell Tumor", "value": 1 }, { "key": "Peripheral Nervous System", "value": 1 }, { "key": "Thyroid", "value": 1 }, { "key": "Vulva/Vagina", "value": 1 } ] } ], "cancer_hotspots": [ { "version": "10-Sep-2021", "total_samples": 758, "t_ref_count": 216348, "t_alt_count": 82259, "n_ref_count": 270, "n_alt_count": 9, "n_depth": 7983, "t_depth": 347845, "somatic": null, "canonical": true, "ensp": "ENSP00000256078", "ccds": "CCDS8703.1", "cdsposition": "35/570", "cdnaposition": "99/1119", "biotype": "protein_coding", "feature": "ENST00000256078", "uniparc": "Upi0000133132", "pick": 1.0, "pub_med_references": null, "oncotree_code": [ { "key": "PAAD", "value": 319 }, { "key": "COAD", "value": 92 }, { "key": "LUAD", "value": 82 }, { "key": "COADREAD", "value": 64 }, { "key": "UEC", "value": 24 }, { "key": "MAAP", "value": 18 }, { "key": "STAD", "value": 16 }, { "key": "READ", "value": 12 }, { "key": "MACR", "value": 10 }, { "key": "BLCA", "value": 9 }, { "key": "SBC", "value": 7 }, { "key": "APAD", "value": 6 }, { "key": "CUP", "value": 6 }, { "key": "CHOL", "value": 5 }, { "key": "ESCA", "value": 5 }, { "key": "UCS", "value": 4 }, { "key": "MOV", "value": 4 }, { "key": "CESC", "value": 4 }, { "key": "EHCH", "value": 3 }, { "key": "PAASC", "value": 3 }, { "key": "PAMPCA", "value": 3 }, { "key": "PCM", "value": 3 }, { "key": "PRCC", "value": 3 }, { "key": "SKCM", "value": 3 }, { "key": "AMPCA", "value": 2 }, { "key": "SEM", "value": 2 }, { "key": "LUNE", "value": 2 }, { "key": "UTUC", "value": 2 }, { "key": "GBM", "value": 2 }, { "key": "AML", "value": 2 }, { "key": "IHCH", "value": 2 }, { "key": "HGNEC", "value": 2 }, { "key": "UAD", "value": 1 }, { "key": "ES", "value": 1 }, { "key": "SBOV", "value": 1 }, { "key": "SCB", "value": 1 }, { "key": "SCLC", "value": 1 }, { "key": "ECAD", "value": 1 }, { "key": "CCOV", "value": 1 }, { "key": "BRCA", "value": 1 }, { "key": "THYM", "value": 1 }, { "key": "GCCAP", "value": 1 }, { "key": "BLAD", "value": 1 }, { "key": "AODG", "value": 1 }, { "key": "UMEC", "value": 1 }, { "key": "URCC", "value": 1 }, { "key": "USC", "value": 1 }, { "key": "VMM", "value": 1 }, { "key": "OCSC", "value": 1 }, { "key": "IPMN", "value": 1 }, { "key": "IMT", "value": 1 }, { "key": "LXSC", "value": 1 }, { "key": "IDC", "value": 1 }, { "key": "MCN", "value": 1 }, { "key": "MDS", "value": 1 }, { "key": "MUP", "value": 1 }, { "key": "NSCLC", "value": 1 }, { "key": "RMS", "value": 1 }, { "key": "HGGNOS", "value": 1 }, { "key": "HCC", "value": 1 }, { "key": "GINET", "value": 1 }, { "key": "GEJ", "value": 1 }, { "key": "PHCH", "value": 1 }, { "key": "PRAD", "value": 1 }, { "key": "LGSOC", "value": 1 } ], "cancer_name": [ { "key": "Pancreatic Adenocarcinoma", "value": 319 }, { "key": "Colon Adenocarcinoma", "value": 92 }, { "key": "Lung Adenocarcinoma", "value": 82 }, { "key": "Colorectal Adenocarcinoma", "value": 64 }, { "key": "Uterine Endometrioid Carcinoma", "value": 24 }, { "key": "Mucinous Adenocarcinoma of the Appendix", "value": 18 }, { "key": "Stomach Adenocarcinoma", "value": 16 }, { "key": "Rectal Adenocarcinoma", "value": 12 }, { "key": "Mucinous Adenocarcinoma of the Colon and Rectum", "value": 10 }, { "key": "Bladder Urothelial Carcinoma", "value": 9 }, { "key": "Small Bowel Cancer", "value": 7 }, { "key": "Cancer of Unknown Primary", "value": 6 }, { "key": "Appendiceal Adenocarcinoma", "value": 6 }, { "key": "Cholangiocarcinoma", "value": 5 }, { "key": "Esophageal Adenocarcinoma", "value": 5 }, { "key": "Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumor", "value": 4 }, { "key": "Mucinous Ovarian Cancer", "value": 4 }, { "key": "Cervical Squamous Cell Carcinoma", "value": 4 }, { "key": "Plasma Cell Myeloma", "value": 3 }, { "key": "Cutaneous Melanoma", "value": 3 }, { "key": "Extrahepatic Cholangiocarcinoma", "value": 3 }, { "key": "Papillary Renal Cell Carcinoma", "value": 3 }, { "key": "Adenosquamous Carcinoma of the Pancreas", "value": 3 }, { "key": "Pancreatobiliary Ampullary Carcinoma", "value": 3 }, { "key": "Ampullary Carcinoma", "value": 2 }, { "key": "High-Grade Neuroendocrine Carcinoma of the Colon and Rectum", "value": 2 }, { "key": "Acute Myeloid Leukemia", "value": 2 }, { "key": "Large Cell Neuroendocrine Carcinoma", "value": 2 }, { "key": "Intrahepatic Cholangiocarcinoma", "value": 2 }, { "key": "Seminoma", "value": 2 }, { "key": "Glioblastoma Multiforme", "value": 2 }, { "key": "Upper Tract Urothelial Carcinoma", "value": 2 }, { "key": "Sarcomatoid Carcinoma of the Urinary Bladder", "value": 1 }, { "key": "Rhabdomyosarcoma", "value": 1 }, { "key": "Serous Borderline Ovarian Tumor", "value": 1 }, { "key": "Small Cell Lung Cancer", "value": 1 }, { "key": "Low-Grade Serous Ovarian Cancer", "value": 1 }, { "key": "Thymoma", "value": 1 }, { "key": "Prostate Adenocarcinoma", "value": 1 }, { "key": "Unclassified Renal Cell Carcinoma", "value": 1 }, { "key": "Perihilar Cholangiocarcinoma", "value": 1 }, { "key": "Uterine Mixed Endometrial Carcinoma", "value": 1 }, { "key": "Urethral Adenocarcinoma", "value": 1 }, { "key": "Uterine Serous Carcinoma/Uterine Papillary Serous Carcinoma", "value": 1 }, { "key": "High-Grade Glioma, NOS", "value": 1 }, { "key": "Adenocarcinoma of the Gastroesophageal Junction", "value": 1 }, { "key": "Anaplastic Oligodendroglioma", "value": 1 }, { "key": "Bladder Adenocarcinoma", "value": 1 }, { "key": "Breast Invasive Ductal Carcinoma", "value": 1 }, { "key": "Clear Cell Ovarian Cancer", "value": 1 }, { "key": "Endocervical Adenocarcinoma", "value": 1 }, { "key": "Ewing Sarcoma", "value": 1 }, { "key": "Gastrointestinal Neuroendocrine Tumors", "value": 1 }, { "key": "Goblet Cell Adenocarcinoma of the Appendix", "value": 1 }, { "key": "Hepatocellular Carcinoma", "value": 1 }, { "key": "Oral Cavity Squamous Cell Carcinoma", "value": 1 }, { "key": "Inflammatory Myofibroblastic Tumor", "value": 1 }, { "key": "Intraductal Papillary Mucinous Neoplasm", "value": 1 }, { "key": "Invasive Breast Carcinoma", "value": 1 }, { "key": "Larynx Squamous Cell Carcinoma", "value": 1 }, { "key": "Melanoma of Unknown Primary", "value": 1 }, { "key": "Mucinous Cystic Neoplasm", "value": 1 }, { "key": "Mucosal Melanoma of the Vulva/Vagina", "value": 1 }, { "key": "Myelodysplastic Syndromes", "value": 1 }, { "key": "Non-Small Cell Lung Cancer", "value": 1 } ], "cancer_type": [ { "key": "Pancreatic Cancer", "value": 324 }, { "key": "Colorectal Cancer", "value": 178 }, { "key": "Non-Small Cell Lung Cancer", "value": 85 }, { "key": "Endometrial Cancer", "value": 30 }, { "key": "Appendiceal Cancer", "value": 25 }, { "key": "Esophagogastric Cancer", "value": 22 }, { "key": "Bladder Cancer", "value": 14 }, { "key": "Hepatobiliary Cancer", "value": 12 }, { "key": "Small Bowel Cancer", "value": 7 }, { "key": "Ovarian Cancer", "value": 7 }, { "key": "Cancer of Unknown Primary", "value": 6 }, { "key": "Ampullary Cancer", "value": 5 }, { "key": "Melanoma", "value": 5 }, { "key": "Cervical Cancer", "value": 5 }, { "key": "Glioma", "value": 4 }, { "key": "Renal Cell Carcinoma", "value": 4 }, { "key": "Mature B-Cell Neoplasms", "value": 3 }, { "key": "Gastrointestinal Neuroendocrine Tumor", "value": 3 }, { "key": "Germ Cell Tumor", "value": 2 }, { "key": "Head and Neck Cancer", "value": 2 }, { "key": "Leukemia", "value": 2 }, { "key": "Breast Cancer", "value": 2 }, { "key": "Soft Tissue Sarcoma", "value": 2 }, { "key": "Small Cell Lung Cancer", "value": 1 }, { "key": "Thymic Tumor", "value": 1 }, { "key": "Prostate Cancer", "value": 1 }, { "key": "Bone Cancer", "value": 1 }, { "key": "Myelodysplastic Syndromes", "value": 1 } ], "tissue_type": [ { "key": "Pancreas", "value": 324 }, { "key": "Bowel", "value": 213 }, { "key": "Lung", "value": 86 }, { "key": "Uterus", "value": 30 }, { "key": "Esophagus/Stomach", "value": 22 }, { "key": "Bladder/Urinary Tract", "value": 14 }, { "key": "Biliary Tract", "value": 11 }, { "key": "Ovary/Fallopian Tube", "value": 7 }, { "key": "Other", "value": 6 }, { "key": "Cervix", "value": 5 }, { "key": "Ampulla of Vater", "value": 5 }, { "key": "CNS/Brain", "value": 4 }, { "key": "Skin", "value": 4 }, { "key": "Kidney", "value": 4 }, { "key": "Lymphoid", "value": 3 }, { "key": "Myeloid", "value": 3 }, { "key": "Breast", "value": 2 }, { "key": "Soft Tissue", "value": 2 }, { "key": "Testis", "value": 2 }, { "key": "Head and Neck", "value": 2 }, { "key": "Liver", "value": 1 }, { "key": "Bone", "value": 1 }, { "key": "Prostate", "value": 1 }, { "key": "Thymus", "value": 1 }, { "key": "Vulva/Vagina", "value": 1 } ] } ], "phylop100way": [ { "version": "13-Apr-2021", "conservation_score": [ "7.746" ] } ], "maxentscan": null }