CNVs were categorized by clinical laboratories as pathogenic, VOUS or benign based on known clinically relevant regions, gene content and inheritance pattern as previously described.5,8 For both deletions and duplications, the genes located within the CNVs were assessed, as well as neighboring genes. Imbalances that involved large genomic segments from the chromosomal backbone coverage were considered to be likely pathogenic if they contained multiple known genes and did not overlap a confirmed benign CNV region. CNVs were classified as pathogenic if the CNV included an autosomal dominant gene known to cause a disease phenotype. The genomic regions associated with known pathogenic and benign CNVs are listed in Supplementary Tables 1–3 and were also deposited into dbVar (nstd45). Because the clinical laboratories that contributed data used different standards for reporting benign CNVs, an accurate assessment of the frequency of these benign CNVs was impossible for this dataset; therefore, benign CNVs identified in cases with otherwise normal array results were not included in this study.
