ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1384C>G (p.Gln462Glu)

dbSNP: rs876657701
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001219639 SCV001391587 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-08-07 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 462 of the MSH2 protein (p.Gln462Glu). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 948392). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency).
GeneDx RCV001664761 SCV001874888 uncertain significance not provided 2021-08-02 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002379829 SCV002696493 likely benign Hereditary cancer-predisposing syndrome 2023-06-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV004010728 SCV004833241 uncertain significance Lynch syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 462 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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