As previously noted [5], uterine and endometrial cancers differed from colorectal cancer, with MSH6 (OR=13.2) and MSH2 (OR=11.9) emerging as the top risk factors, followed by MLH1 and PMS2. Separating MSH2 missense variants by their functional status, those with abnormal function scores (by DMS or SpliceAI) were significantly associated with both CRC (OR=2.53, 95%CI:[1.04, 6.15], P=0.04) and EC (OR=5.56, 95%CI:[2.24,13.8], P=2.2×10−4), though with smaller effects than truncating P/LP variants’ (Fig. 4). Here, MSH6 is linked to colorectal cancer.