ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.409G>C (p.Gly137Arg) (rs587781795)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130057 SCV000184884 likely benign Hereditary cancer-predisposing syndrome 2017-07-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Color RCV000130057 SCV000690108 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
GeneDx RCV000679311 SCV000292616 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.409G>C at the cDNA level, p.Gly137Arg (G137R) at the protein level, and results in the change of a Glycine to an Arginine (GGT>CGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. MSH2 Gly137Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the connector domain (L?tzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Gly137Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000202282 SCV000595834 uncertain significance not specified 2017-03-22 criteria provided, single submitter clinical testing
Invitae RCV000196356 SCV000254423 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 137 of the MSH2 protein (p.Gly137Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs587781795, ExAC 0.001%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 141500). 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 C0"). 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202282 SCV000257189 uncertain significance not specified no assertion criteria provided research
PreventionGenetics RCV000679311 SCV000806041 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202282 SCV000601477 uncertain significance not specified 2017-04-10 criteria provided, single submitter clinical testing

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