ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2043A>C (p.Gln681His)

dbSNP: rs730881763
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814388 SCV000954796 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-10-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002422813 SCV002723064 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-17 criteria provided, single submitter clinical testing The p.Q681H variant (also known as c.2043A>C), located in coding exon 13 of the MSH2 gene, results from an A to C substitution at nucleotide position 2043. The glutamine at codon 681 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003324799 SCV004030645 uncertain significance not provided 2023-08-08 criteria provided, single submitter clinical testing Published functional studies suggest a neutral effect: restored mismatch repair (MMR) function in a MSH2 knockout cell line (Jia et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18822302, 21120944, 33357406)
All of Us Research Program, National Institutes of Health RCV004001761 SCV004825228 uncertain significance Lynch syndrome 2023-12-01 criteria provided, single submitter clinical testing

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