ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1330C>T (p.Arg444Cys)

dbSNP: rs1675070099
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001214776 SCV001386480 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-06-28 criteria provided, single submitter clinical testing 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 444 of the MSH2 protein (p.Arg444Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine.
Ambry Genetics RCV002561854 SCV003582114 likely benign Inborn genetic diseases 2021-10-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.

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