ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2697G>T (p.Met899Ile)

dbSNP: rs878853813
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233718 SCV000284159 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-04-21 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 899 of the MSH2 protein (p.Met899Ile). 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: 237391). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein 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 RCV001016339 SCV001177286 likely benign Hereditary cancer-predisposing syndrome 2022-09-01 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001262889 SCV001440925 uncertain significance Breast carcinoma 2019-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003469138 SCV004196846 uncertain significance Lynch syndrome 1 2023-05-10 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998762 SCV004842690 uncertain significance Lynch syndrome 2024-01-11 criteria provided, single submitter clinical testing

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