ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1282A>G (p.Lys428Glu) (rs761822293)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538584 SCV000624634 uncertain significance Hereditary nonpolyposis colon cancer 2017-05-04 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 428 of the MSH6 protein (p.Lys428Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs761822293, ExAC 0.001%). This variant has been reported in an individual with familial colorectal cancer (PMID: 28195393). 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 variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567668 SCV000662523 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Color RCV000567668 SCV000908372 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing

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