ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2910G>C (p.Trp970Cys) (rs765411990)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460406 SCV000551277 uncertain significance Lynch syndrome 2016-12-29 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 970 of the MSH6 protein (p.Trp970Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is present in population databases (rs765411990, ExAC 0.02%) but has not been reported in the literature in individuals with a MSH6-related disease. 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. 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.
Ambry Genetics RCV001016938 SCV001177947 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-11 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence;Structural Evidence

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