The study looked at the identification of genetic variants in Chinese families with suspected Lynch syndrome and colorectal cancer. Samples from three probands were analyzed by immunohistochemistry and whole-exome sequencing. Two known missense variants in the PMS2 gene (c.1847T>C and c.2444C>T) and a new frameshift variant in the MSH2 gene (c.579delG) were identified. In silico analyzes indicated that the c.2444C>T variant in PMS2 locally alters the protein structure, and the c.579delG variant in MSH2 leads to significant protein truncation and loss of domains. Variants in PMS2 were classified as variants of uncertain significance, while a novel variant in MSH2 was designated as likely pathogenic.