ClinVar

Description

Variant summary: MSH2 c.192C>G (p.Ile64Met) results in a conservative amino acid change located in the DNA mismatch repair protein MutS-like, N-terminal doomain (IPR007695) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 230350 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.192C>G has been reported in the literature in an individual affected with endometrial carcinomas who carried a pathogenic PMS2 vairant (Rosa_2020). This report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.