ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.229C>T (p.Arg77Trp) (rs745442468)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525000 SCV000624743 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 77 of the MSH6 protein (p.Arg77Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 455187). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000561728 SCV000662376 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759131 SCV000888252 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing

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