ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2177T>A (p.Phe726Tyr) (rs574358605)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524133 SCV000551268 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 726 of the MSH6 protein (p.Phe726Tyr). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is present in population databases (rs574358605, ExAC 0.002%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 89259). 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. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000568729 SCV000662472 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000662512 SCV000785051 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-03-27 criteria provided, single submitter clinical testing
Color RCV000568729 SCV000908391 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-17 criteria provided, single submitter clinical testing

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