The distribution of BRAF variant subtypes and classes in our cohort was different than that in other types of cancer, such as melanoma, thyroid cancers, CRC, and NSCLC (eFigure 4 in Supplement 1).10 We propose that the BRAF variant patterns are at least in part a product of selection during tumor initiation for an ideal level of signaling, which is shaped by variations in the function of particular BRAF variants, BRAF protein levels, and cellular responses to oncogenic BRAF.25 Here, BRAF is linked to colorectal carcinoma.