ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2392C>G (p.Leu798Val) (rs587779238)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572114 SCV000673986 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-06 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 evidence
Invitae RCV000629860 SCV000750816 uncertain significance Hereditary nonpolyposis colon cancer 2017-12-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 798 of the MSH6 protein (p.Leu798Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827  and the Leiden Open-source Variation Database (PMID: 21520333, 23621914). ClinVar contains an entry for this variant (Variation ID: 89278). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be deleterious (PMID: 23621914). However, 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 C15"). 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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