The identified Cys333Tyr variant, along with the overrepresentation of cysteine‐affecting variants in DLL4, suggests a mechanism similar to that observed in Alagille syndrome, CADASIL, and Marfan syndrome, where pathogenicity is linked to cysteine substitutions within epidermal growth factor (EGF)‐like domains [11, 12, 13, 14]. Here, NOTCH3 is linked to Marfan syndrome.