Novel (p.N143D) and previously reported (p.H144R) variants were identified close to the exonuclease domain of POLE. All six MLH3 variants (p.A1394T, p.N1147I, p.L1111F, p.D1049N, p.L880V, and p.F168S) were in cases with MSS CRC before age 60 (Supplementary Figures 3 and 4). The gene discussed is POLE; the disease is colorectal carcinoma.