Stringent allele filtering thresholds (ExAC < 0.1% MAF) and CADD score based pathogenicity ranking (scaled CADD scores > 15) are particularly useful in analyzing intrinsically variable genes such as KMT2D and MYH6. Such filtering allowed us to identify two recessive MYH6 mutations in a family with pleiotropic cardiac malformations including HLHs, septal defects and aortopathy. The gene discussed is KMT2D; the disease is hypoplastic left heart syndrome.