Submissions for variant NM_004985.5(KRAS):c.34G>C (p.Gly12Arg)

dbSNP: rs121913530

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001356365	SCV002497210	pathogenic	not provided	2022-02-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513010	SCV003021276	likely pathogenic	RASopathy	2022-07-04	criteria provided, single submitter	clinical testing	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. 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. 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. ClinVar contains an entry for this variant (Variation ID: 12579). This variant has not been reported in the literature in individuals affected with KRAS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 12 of the KRAS protein (p.Gly12Arg).
OMIM	RCV000013407	SCV000033654	pathogenic	Squamous cell lung carcinoma	1984-02-17	no assertion criteria provided	literature only
OMIM	RCV000013408	SCV000033655	pathogenic	Malignant tumor of urinary bladder	1984-02-17	no assertion criteria provided	literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154401	SCV000204068	pathogenic	Non-small cell lung carcinoma	2014-08-28	no assertion criteria provided	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356365	SCV001551511	pathogenic	not provided		no assertion criteria provided	clinical testing