ClinVar Miner

Submissions for variant NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) (rs121913529)

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Total submissions: 29
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000272938 SCV000329383 pathogenic not provided 2019-11-13 criteria provided, single submitter clinical testing The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 18813118, 23096712, 23437064, 24803665, 15093544, 19847165, 22264792, 21451123, 21502497, 18308936, 27362559, 11323676, 26521233, 20805368, 22683711, 17910045, 19075190, 21680795, 30355600, 30394973, 30443000)
Invitae RCV000548006 SCV000659085 pathogenic Rasopathy 2017-06-30 criteria provided, single submitter clinical testing 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.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000029215 SCV001736991 pathogenic Epidermal nevus syndrome criteria provided, single submitter clinical testing
OMIM RCV000013411 SCV000033658 pathogenic Carcinoma of pancreas 2012-06-10 no assertion criteria provided literature only
OMIM RCV000013412 SCV000033659 pathogenic Neoplasm of stomach 2012-06-10 no assertion criteria provided literature only
OMIM RCV000022799 SCV000044088 pathogenic Epidermal nevus 2012-06-10 no assertion criteria provided literature only
OMIM RCV000029214 SCV000051860 pathogenic Nevus sebaceous 2012-06-10 no assertion criteria provided literature only
OMIM RCV000029215 SCV000051861 pathogenic Epidermal nevus syndrome 2012-06-10 no assertion criteria provided literature only
OMIM RCV000144969 SCV000191996 pathogenic Juvenile myelomonocytic leukemia 2012-06-10 no assertion criteria provided literature only
OMIM RCV000144970 SCV000191997 pathogenic RAS-associated autoimmune leukoproliferative disorder 2012-06-10 no assertion criteria provided literature only
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000144969 SCV000198478 pathogenic Juvenile myelomonocytic leukemia 2014-08-28 no assertion criteria provided clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150896 SCV000198479 pathogenic Non-small cell lung cancer 2014-08-28 no assertion criteria provided clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150897 SCV000198480 pathogenic Neoplasm of ovary 2014-08-28 no assertion criteria provided clinical testing 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).
Database of Curated Mutations (DoCM) RCV000426369 SCV000504481 pathogenic Neoplasm of the large intestine 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433573 SCV000504482 likely pathogenic Acute myeloid leukemia 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443973 SCV000504483 pathogenic Neoplasm of the thyroid gland 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425250 SCV000504484 likely pathogenic Lung carcinoma 2016-03-10 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000150897 SCV000504485 pathogenic Neoplasm of ovary 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000150896 SCV000504486 pathogenic Non-small cell lung cancer 2016-03-10 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000013411 SCV000504487 not provided Carcinoma of pancreas 2016-03-10 no assertion provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000029214 SCV000611562 pathogenic Nevus sebaceous 2012-10-25 no assertion criteria provided literature only
OMIM RCV000585796 SCV000693723 pathogenic Cerebral arteriovenous malformation 2018-03-06 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000662266 SCV000784594 likely pathogenic Vascular Tumors Including Pyogenic Granuloma 2015-02-19 no assertion criteria provided literature only
Thoracic Oncology Service,Memorial Sloan Kettering Cancer Center RCV000150896 SCV000882686 pathogenic Non-small cell lung cancer no assertion criteria provided research
Laboratory for Clinical Genomics and Advanced Technology,Dartmouth-Hitchcock Medical Center RCV000013411 SCV000882700 pathogenic Carcinoma of pancreas 2019-02-07 no assertion criteria provided research Variant causes impairment of the intrinsic GTPase activity of KRAS and subsequent activation of downstream signaling pathways that drive cancer growth.
Arin Greene Laboratory,Boston Children's Hospital, Harvard Medical School RCV000585796 SCV000992585 pathogenic Cerebral arteriovenous malformation no assertion criteria provided research
University Health Network,Princess Margaret Cancer Centre RCV000856666 SCV000999192 pathogenic Primary low grade serous adenocarcinoma of ovary 2019-11-04 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000272938 SCV001550138 uncertain significance not provided no assertion criteria provided clinical testing
Hematopathology,The University of Texas M.D. Anderson Cancer Center RCV000433573 SCV001571657 pathogenic Acute myeloid leukemia 2018-03-30 no assertion criteria provided clinical testing

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