These observations held when we analyzed the rare potentially damaging missense variants in LRP1 associated with CHD (p = 0.000226), CTD (p = 0.00309), LVOTO (p = 0.0341), and AVSD (p = 0.0121) (Supplementary Table S5). This evidence concerns the gene LRP1 and familial atrioventricular septal defect.