ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.374C>T (p.Pro125Leu) (rs876659113)

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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 RCV000218398 SCV000275188 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-24 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505865 SCV000601475 uncertain significance not specified 2017-05-05 criteria provided, single submitter clinical testing
Invitae RCV001219759 SCV001391712 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-05-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 125 of the MSH2 protein (p.Pro125Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231360). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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