ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1609A>G (p.Lys537Glu) (rs753276270)

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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 RCV000572199 SCV000673926 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Color RCV000572199 SCV000685207 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-03 criteria provided, single submitter clinical testing
Invitae RCV000686466 SCV000813985 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-21 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 537 of the MSH6 protein (p.Lys537Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs753276270, ExAC 0.001%). While this variant has been published in the literature (PMID: 25194673), it has not been reported in the germline of an individual with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 485856). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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