Two of the variants of unknown origin (ie, no evidence of tumor origin) are clinically significant, with the NRAS Q61R mutation (P8) being a standard-of-care biomarker to predict resistance to anti–estimated glomerular filtration rate therapy in colorectal carcinoma (level R1 in OncoKB21) and the TSC1 Q797del (P6), a standard-of-care biomarker to predict response to everolimus (level 1 in OncoKB21). This evidence concerns the gene TSC1 and colorectal carcinoma.