MSH2 c.1022T>C, p.Leu341Pro is a founder pathogenic variation and a major cause of Lynch syndrome in the North of France.

Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well-known genes such as the DNA-mismatch repair (MMR) genes involved in Lynch syndrome. We report the characterization of a variant in MSH2: c.1022T>C, which was identified in 20 apparently unrelated families living in the North of France.