ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1937A>C (p.Tyr646Ser) (rs35045067)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228026 SCV000284037 uncertain significance Lynch syndrome 2015-12-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with serine at codon 646 of the MLH1 protein (p.Tyr646Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. 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 is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000575674 SCV000673835 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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