ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1159C>G (p.Leu387Val) (rs751249745)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629973 SCV000750929 uncertain significance Hereditary nonpolyposis colon cancer 2018-03-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 387 of the MSH2 protein (p.Leu387Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with primary astrocytoma (PMID: 24073290). It has also been observed in an individual in the UMD-MSH2 database (PMID: 23729658). However, in that individual a pathogenic allele was also identified in PMS2 which suggests that this c.1159C>G variant was not the primary cause of 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: "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.
Ambry Genetics RCV001010046 SCV001170189 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-19 criteria provided, single submitter clinical testing Insufficient evidence

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