ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.127T>G (p.Tyr43Asp)

dbSNP: rs786202731
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679285 SCV000805993 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010721 SCV001170958 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-21 criteria provided, single submitter clinical testing The p.Y43D variant (also known as c.127T>G), located in coding exon 1 of the MSH2 gene, results from a T to G substitution at nucleotide position 127. The tyrosine at codon 43 is replaced by aspartic acid, an amino acid with highly dissimilar 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. In addition, this alteration is predicted to be deleterious by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001861867 SCV002300913 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-11-24 criteria provided, single submitter clinical testing 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. ClinVar contains an entry for this variant (Variation ID: 560786). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 43 of the MSH2 protein (p.Tyr43Asp).
All of Us Research Program, National Institutes of Health RCV004004219 SCV004837655 uncertain significance Lynch syndrome 2023-11-30 criteria provided, single submitter clinical testing

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