ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.897G>T (p.Lys299Asn) (rs755878786)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527690 SCV000625019 uncertain significance Hereditary nonpolyposis colon cancer 2017-03-08 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 299 of the MSH6 protein (p.Lys299Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs755878786, ExAC 0.006%) but 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000575082 SCV000662579 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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