ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1892G>A (p.Arg631Lys)

dbSNP: rs1361816581
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547904 SCV000625328 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 631 of the MSH2 protein (p.Arg631Lys). 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: 455532). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. 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 RCV000568306 SCV000669747 likely benign Hereditary cancer-predisposing syndrome 2022-07-06 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.
Color Diagnostics, LLC DBA Color Health RCV000568306 SCV000690026 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-12 criteria provided, single submitter clinical testing
GeneDx RCV001572130 SCV001796714 uncertain significance not provided 2023-05-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies suggest no impact on function: demonstrates sensitivity to 6-TG similar to wild type (Jia et al., 2020); Observed in an unaffected control in a case control study assessing melanoma and individuals with multiple cancers (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 18822302, 21120944, 29641532, 33357406)
Sema4, Sema4 RCV000568306 SCV002534422 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002481753 SCV002783550 uncertain significance Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2 2022-04-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004003740 SCV004829807 uncertain significance Lynch syndrome 2023-03-28 criteria provided, single submitter clinical testing

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