We observed a significant excess of rare damaging LRP1 variants (missense variants + loss of function) in all CHD (OR = 2.22, p = 0.000192), conotruncal defects (CTDs) (OR = 2.37, p = 0.00177), left outflow tract obstructions (LVOTO, OR = 1.86, p = 0.0307), and AVSD (OR = 3.14, p = 0.0194) compared with controls (Figure 5A,B, Supplemental Table S4). Here, LRP1 is linked to familial atrioventricular septal defect.