ClinVar Miner

Submissions for variant NM_001258281.1(MSH2):c.-31+78_-31+79delinsTT (rs1060501996)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456279 SCV000548156 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 21 of the MSH2 protein (p.Arg21Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). While this variant has not been reported in the literature in individuals with an MSH2-related disease, a different nucleotide change (c.62G>T) that results in the same amino acid change (p.Arg21Leu) has been reported in an individual in the Universal Mutation Database (PMID: 23729658). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect 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 RCV001025005 SCV001187110 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-24 criteria provided, single submitter clinical testing Insufficient evidence

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