These findings implicated CELSR1 as a susceptibility gene for both BAV and HLHS, and MYO15A as an HLHS modifier; suggested a primary aortic valve developmental defect as a mechanism for HLHS; supported oligogenic, common-pathway underpinnings of sporadic HLHS, and highlighted the value of WGS for identification of non-coding variants that disrupt canonical transcription factor binding sites. Here, CELSR1 is linked to hypoplastic left heart syndrome.