When we tested the association with CRC risk for all predicted pathogenic variants within a gene using gene-based MiST testing, we found that the combined burden of rare predicted pathogenic variants in the APC (P = .0007), MSH3 (P = .0216), and MLH1 (P = .0362) genes increased CRC risk, but these associations were driven by a single rare variant per gene. This evidence concerns the gene APC and colorectal carcinoma.