ClinVar

Description

Variant summary: MSH2 c.2267C>G (p.Thr756Ser) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, C-terminal of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.9e-05 in 277176 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.2267C>G, has been reported in the literature in an individual affected with endometrial carcinoma and was classified as a VUS (Ring_2016). This report does not provide an unequivocal conclusion about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.