ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.251C>T (p.Ala84Val) (rs878853717)

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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 RCV000491394 SCV000580194 likely benign Hereditary cancer-predisposing syndrome 2017-09-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign)
Color RCV000491394 SCV000905263 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-28 criteria provided, single submitter clinical testing
Invitae RCV000229669 SCV000283754 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 84 of the MSH6 protein (p.Ala84Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a MSH6-related disease. This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 237159). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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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