The lack of phenotype in the double heterozygous knock-in mice could be due to genetic background effects, a phenomenon that is firmly established for CHD.26 Although KdrG347W/G347W exhibited no morphological abnormalities, mice homozygous for the orthologous variant to the familial KDR-p.(Gly537Arg) variant (KdrG535R/G535R) died during embryonic development and recapitulate the phenotype of constitutive Kdr knockout mice,16 underscoring the causality and severity of this variant. This evidence concerns the gene KDR and coronary artery disorder.