The germline MLH1 c.2054 C>T mutation disrupts DNA mismatch repair and is detectable by digital PCR.

Germline *MLH1* c.2054 C>T variant: functional pathogenicity validation and detection by digital PCR

This Cancer Letters study describes four colorectal cancer patients carrying the same MLH1 c.2054 C>T variant, initially discordantly classified despite a strong family history. The authors functionally demonstrate that this variant disrupts DNA mismatch repair, validating its pathogenicity, and develop a digital PCR detection method applicable in clinical practice.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Reclassifying discordant MLH1 variants using functional data is exactly what laboratories need for difficult cases. Pairing this with a digital PCR detection method adds immediate practical value for teams managing this recurrent variant.

Clinical impact: 3/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 0/1 · Publication status: 1/1 → Total: 7/10