ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1052T>C (p.Met351Thr)

dbSNP: rs1553353246
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000580084 SCV000684899 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 351 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH2-related disorders 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001295389 SCV001484309 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-02-19 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 351 of the MSH2 protein (p.Met351Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 489909). This variant is not present in population databases (ExAC no frequency).

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