For CRC, the significance of VUS remains uncertain if MLH1 promoter methylation and/or BRAF testing are positive, if results for both tests are unavailable, or if IHC shows an unusual staining pattern (i.e., isolated loss of MLH1) (Supplementary Table 2, INT2GRATE CRC Codes II-V to II-VIII). This evidence concerns the gene BRAF and colorectal carcinoma.