Submissions for variant NM_004985.5(KRAS):c.34G>T (p.Gly12Cys)

dbSNP: rs121913530

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003654176	SCV004501632	likely pathogenic	RASopathy	2023-02-23	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 12578). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 12 of the KRAS protein (p.Gly12Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KRAS-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KRAS protein function. Experimental studies have shown that this missense change affects KRAS function (PMID: 16051643). This variant disrupts the p.Gly12 amino acid residue in KRAS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17704260, 26242988). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM	RCV000013406	SCV000033653	pathogenic	Lung carcinoma	2001-09-15	no assertion criteria provided	literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038265	SCV000061934	pathogenic	Non-small cell lung carcinoma	2007-12-07	no assertion criteria provided	clinical testing
Laboratory of Translational Genomics, National Cancer Institute	RCV000119791	SCV000154263	not provided	Endometrial carcinoma		no assertion provided	not provided
Institute of Medical Sciences, Banaras Hindu University	RCV001292543	SCV001481125	pathogenic	Gallbladder cancer	2020-10-30	no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355787	SCV001550769	pathogenic	not provided		no assertion criteria provided	clinical testing
Salgia Laboratory, City of Hope	RCV000431049	SCV003804197	pathogenic	Lung adenocarcinoma		no assertion criteria provided	clinical testing
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University	RCV003996092	SCV004042813	likely pathogenic	Lung cancer		no assertion criteria provided	clinical testing