Here, we comprehensively characterized VUS patterns among 3,980 individuals with a documented first primary early-onset colorectal cancer [we have previously described the cohort in Seagle and colleagues (4)], which includes 1,001 individuals identifying as non-White (25.2%), who uniformly underwent germline genetic testing for APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53 by a nationwide clinical testing laboratory. Here, PMS2 is linked to colorectal cancer.