ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.320C>T (p.Pro107Leu) (rs878853732)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234256 SCV000283790 uncertain significance Lynch syndrome 2015-11-23 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 107 of the MSH6 protein (p.Pro107Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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 RCV000562799 SCV000670055 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000590544 SCV000695843 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.320C>T (p.Pro107Leu) variant located in the PWWP domain (via InterPro) involves the alteration of a conserved nucleotide, which 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. A clinical diagnostic laboratory reports the variant with a classification of "uncertain significance." Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance."

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