ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1450G>A (p.Glu484Lys) (rs587782706)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199811 SCV000254276 uncertain significance Lynch syndrome 2016-01-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 484 of the MSH6 protein (p.Glu484Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature as a germline variant in individuals with a MSH6-related disease. General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), and algorithms developed specifically for the MSH6 gene (PMID: 22949387, 23621914), all suggest that this missense change is likely to be disruptive. However, these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change that is predicted to disrupt protein function. However, its clinical relevance remains uncertain. For these reason, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001011654 SCV001172001 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing Insufficient evidence

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