ClinVar

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 697 of the MSH2 protein (p.Cys697Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pancreatic cancer and urothelial carcinoma, as well as an individual undergoing genetic testing for Lynch syndrome (PMID: 28514183, 31111311). ClinVar contains an entry for this variant (Variation ID: 187518). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is expected to disrupt MSH2 function. Experimental studies have shown that this missense change affects MSH2 function (PMID: 6951660). This variant disrupts the p.Cys697 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9298827, 16327991, 17101317, 18951462, 22102614). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.