In a multi-center exome sequencing study of various CHD that focused on loss-of-function variants and included parental sequencing data enabling de novo variant identification, the TOF sub-group drove a significant genome-wide burden finding (p-value ≤ 1.3 × 10–6) of de novo and ultra-rare inherited (allele frequency ≤ 1 × 10–5) heterozygous truncating variants for a novel gene, FLT4 (Jin et al., 2017). Here, FLT4 is linked to coronary artery disorder.