This large study of more than 49,000 individuals (mean age, 57 years; 55% female) showed that 441 (0.9%) had a pathogenic or likely pathogenic variant associated with one of the three genomic conditions: familial hypercholesterolemia, n=131 (0.3%); hereditary breast and ovarian cancer syndrome, n=235 (0.5%); and Lynch syndrome, n=76 (0.2%). Patients with the variants had a greater risk for the associated disease: familial hypercholesterolemia, 21.4% of carriers versus 9.4% of noncarriers developed atherosclerotic cardiovascular disease; hereditary breast and ovarian cancer syndrome, 27.6% of female carriers versus 7.7% of female noncarriers developed associated cancers; and Lynch syndrome, 22.4% of carriers versus 1.9% of noncarriers developed colorectal or uterine cancer.