ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2744C>G (p.Ala915Gly) (rs766427609)

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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 RCV000561147 SCV000664871 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000590239 SCV000695826 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.2744C>G (p.Ala915Gly) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 120742 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000793228 SCV000932571 uncertain significance Hereditary nonpolyposis colon cancer 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 915 of the MSH6 protein (p.Ala915Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 480919). 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: "Probably 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.

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