ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2882G>C (p.Arg961Thr) (rs587781458)

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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 RCV000223015 SCV000273177 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000539358 SCV000624799 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 961 of the MSH6 protein (p.Arg961Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs587781458, ExAC 0.002%) but has not been reported in the literature in individuals with a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 229829). 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: "Deleterious"; PolyPhen-2: "Probably 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.
Color RCV000223015 SCV000908405 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-26 criteria provided, single submitter clinical testing

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