ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2906A>T (p.Tyr969Phe) (rs63749919)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129763 SCV000184570 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000204094 SCV000259463 uncertain significance Lynch syndrome 2015-12-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with phenylalanine at codon 969 of the MSH6 protein (p.Tyr969Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is present in population databases (rs63749919, ExAC <0.01%) but has not been reported in the literature in individuals with a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 141296). 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 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.
Counsyl RCV000410024 SCV000488897 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-07-14 criteria provided, single submitter clinical testing

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