MSH6 encodes a protein in the DNA mismatch repair system, which fixes errors made during DNA replication. Partnering with MSH2, it forms a complex that recognizes and helps correct mismatched DNA bases, keeping the genetic code stable. Inherited mutations in MSH6 cause Lynch syndrome (hereditary nonpolyposis colorectal cancer), raising the risk of colorectal, endometrial, ovarian, and other cancers, while mutations in both copies lead to constitutional mismatch repair deficiency. Because faulty mismatch repair drives tumor development and produces microsatellite instability, MSH6 acts as a tumor suppressor, and cancers with such repair defects often respond well to immune checkpoint inhibitor therapy.
MSH6 encodes a DNA mismatch-repair protein that partners with MSH2 to maintain genomic stability; inherited pathogenic variants cause Lynch syndrome, while biallelic variants cause constitutional mismatch repair deficiency.
BP4 supporting: MSH6 HCI prior 0.0236 is below the VCEP threshold of <0.11. VUS: no pathogenic or benign combination rule was satisfied by the adjudicated criteria.
African/African American 3 / 74,898 |
0.004% |
European (non-Finnish) 33 / 1,179,996 |
0.0028% |
Admixed American 1 / 59,976 |
0.0017% |
South Asian 1 / 91,088 |
0.0011% |
European (non-Finnish) 4 / 128,982 |
0.0031% |
Admixed American 1 / 35,410 |
0.0028% |
