ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2128G>T (p.Ala710Ser)

dbSNP: rs1558519878
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000771721 SCV000904378 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-23 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 710 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with gastrointestinal cancer (PMID: 23760103). 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 RCV002533997 SCV002976635 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-12-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 710 of the MSH2 protein (p.Ala710Ser). 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: 627845). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 95%. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003736903 SCV004565096 uncertain significance not provided 2023-05-15 criteria provided, single submitter clinical testing The MSH2 c.2128G>T; p.Ala710Ser variant (rs1558519878), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 627845). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.757). Due to limited information, the clinical significance of this variant is uncertain at this time.

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