NOTCH1 and congenital heart disease: Recently, the increased use of exome sequencing and genome sequencing (GS) has demonstrated that NOTCH1 variants are a more frequent cause of congenital heart disease (CHD) than was previously recognized, particularly in the context of tetralogy of Fallot (TOF), where deleterious NOTCH1 variants have been deemed responsible for 4–5% of cases [15, 20, 21].