Recently, disease modeling of GATA4 and TBX5 pathogenic variants in human iPSC-derived CM and iPSCs-derived EC from patients with bicuspid aortic valve and calcific aortic valve disease with NOTCH1 haploinsufficiency have predicted that CHD-linked GRN is sensitive to gene dosage71–73. This evidence concerns the gene NOTCH1 and aortic valve calcification.