ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2209A>G (p.Arg737Gly)

dbSNP: rs1573570754
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798577 SCV000938200 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-07-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 737 of the MSH2 protein (p.Arg737Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 644619). 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 disruptive. 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.
Ambry Genetics RCV001014790 SCV001175546 likely benign Hereditary cancer-predisposing syndrome 2021-11-15 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.
Cancer Genomics Group, Japanese Foundation For Cancer Research RCV001030714 SCV001193636 uncertain significance Hereditary breast ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
GeneDx RCV001592981 SCV001826291 uncertain significance not provided 2020-08-03 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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