ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3652G>C (p.Gly1218Arg) (rs776407427)

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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 RCV000222748 SCV000276520 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Invitae RCV000231815 SCV000283812 uncertain significance Lynch syndrome 2016-03-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1218 of the MSH6 protein (p.Gly1218Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a patient suspected to have Lynch syndrome (PMID: 22495361), although specific details about this individuals personal and/or family history were not provided. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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