ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1885G>T (p.Asp629Tyr) (rs1064795030)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554356 SCV000624699 uncertain significance Hereditary nonpolyposis colon cancer 2017-09-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 629 of the MSH6 protein (p.Asp629Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency) and 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000615160 SCV000712782 uncertain significance not specified 2017-01-11 criteria provided, single submitter clinical testing The p.Asp629Tyr variant in MSH6 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p .Asp62Tyr variant is uncertain.

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