ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1708A>G (p.Ile570Val) (rs61748081)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205186 SCV000261332 uncertain significance Lynch syndrome 2015-10-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 570 of the MSH6 protein (p.Ile570Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs61748081, ExAC 0.01%) but has not been reported in affected individuals in the literature. General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) and an algorithm developed specifically for MSH6 (PMID: 23621914) all suggest that this missense change is likely to be tolerated, although these predictions have not been confirmed by published functional studies. In addition, the valine amino acid residue is found in multiple mammalian species, also suggesting that this missense change does not adversely affect protein function. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001012760 SCV001173254 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-08 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV001012760 SCV001347870 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-29 criteria provided, single submitter clinical testing

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