Submissions for variant NM_004985.5(KRAS):c.182A>G (p.Gln61Arg)

dbSNP: rs121913240

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038257	SCV000061926	pathogenic	Noonan syndrome	2009-11-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001209740	SCV001381189	uncertain significance	RASopathy	2019-05-23	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine with arginine at codon 61 of the KRAS protein (p.Gln61Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). This variant has been reported as a recurrent variant in tumors (PMID: 26985062); however, this variant has not been reported as a germline variant in affected individuals. ClinVar contains an entry for this variant (Variation ID: 45115). This variant is not present in population databases (ExAC no frequency).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813342	SCV002060771	uncertain significance	Noonan syndrome and Noonan-related syndrome	2021-02-03	criteria provided, single submitter	clinical testing
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University	RCV003996395	SCV004042811	likely pathogenic	Lung cancer		no assertion criteria provided	clinical testing