Fig. 5

Frequency of high-confidence splice-disrupting variants in CHD genes. One hundred thirty three confirmed and high-confidence splice disrupting variants in CHD genes were identified in the 1101 CHD patients—Discovery (n = 106), Validation (n = 48), and Extension (n = 947) cohorts. Variants were mapped to their closest annotated wild-type splice site within their corresponding gene. Canonical splice regions are highlighted in gray. a Variant position: Intronic variants > 10 bp from a splice junction accounted for 49% of all variants. b SpliceAI Δ variant scores: Splice-disrupting variants showed high variability in SpliceAI scores. Putatively disease-causing splice-disrupting variants in Tier 1 CHD genes were found in c 4% of TOF probands, and d 5% of TGA probands without an explained genetic etiology, with non-canonical variants representing a majority of splice disrupting variants. TOF, tetralogy of Fallot; TGA, Transposition of the great arteries; SNV, single-nucleotide variant; indel, insertion-deletion