ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1868C>T (p.Pro623Leu) (rs63750462)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000074693 SCV000551261 uncertain significance Hereditary nonpolyposis colon cancer 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 623 of the MSH6 protein (p.Pro623Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (rs63750462, ExAC no frequency). This variant has been reported in individuals affected with endometrial cancer (PMID: 16885385, 15354210). An experimental study has shown that this missense change does not have any adverse impact on the repair activity of MSH6 and does not distrust the interaction of the MSH6 with MSH2 in vitro (PMID: 15354210). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV001186403 SCV001352800 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-07 criteria provided, single submitter clinical testing

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