ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.155T>C (p.Leu52Pro)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002405387 SCV002709859 likely benign Hereditary cancer-predisposing syndrome 2022-07-03 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.
Invitae RCV003759682 SCV004501037 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-03-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004007332 SCV004825427 uncertain significance Lynch syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 52 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 1/233200 chromosomes 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.

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