ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2161A>G (p.Arg721Gly) (rs537604099)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132526 SCV000187623 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000469296 SCV000551252 uncertain significance Lynch syndrome 2016-04-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 721 of the MSH6 protein (p.Arg721Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 143007). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000469296 SCV000837893 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000132526 SCV000903780 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing

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