MLH1 encodes a DNA mismatch repair protein that, together with partners such as PMS2, corrects errors that arise during DNA replication. Loss of this repair function leads to the accumulation of mutations, particularly in repetitive microsatellite sequences, and tumors with defective MLH1 typically show high microsatellite instability. Germline mutations in MLH1 cause Lynch syndrome (hereditary non-polyposis colorectal cancer), which strongly predisposes to colorectal, endometrial, ovarian, and other cancers, while biallelic mutations cause constitutional mismatch repair deficiency (CMMRD). Because it normally protects against cancer by maintaining genomic stability, MLH1 acts as a tumor suppressor, and mismatch-repair-deficient tumors often respond well to immunotherapy.
MLH1 encodes a DNA mismatch repair protein whose loss of function causes Lynch syndrome and, when both alleles are affected, constitutional mismatch repair deficiency.
VUS: BP4 supporting is met because SpliceAI's maximum delta score is 0.099, at or below the VCEP no-impact cutoff of 0.1.
Remaining individuals 3 / 62,340 |
0.0048% |
European (non-Finnish) 34 / 1,176,042 |
0.0029% |
African/African American 1 / 74,766 |
0.0013% |
African/African American 1 / 16,256 |
0.0062% |
