ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1478A>T (p.Gln493Leu) (rs376990143)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458047 SCV000548176 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine with leucine at codon 493 of the MSH2 protein (p.Gln493Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is present in population databases (rs376990143, ExAC 0.01%) but has not been reported in the literature in individuals with an MSH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573378 SCV000673869 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-20 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000573378 SCV001340984 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-18 criteria provided, single submitter clinical testing

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