POLE and colorectal carcinoma: Variants classified as VUS by ACMG criteria include candidates suggestive of being pathogenic, such as POLE p.H144R (MSS CRC at 48 years), BLM p.Y1044C (MSS CRC at 48 and 72 years), and MLH1 p.R100P (MSI-H CRC at 28 years).