We collected 2,603 samples in 13 genetic-disorder categories: neurodevelopmental disorders, blindness, deafness, immunodeficiency, movement disorders, muscle disorders, renal disorders, craniofacial anomalies, disorders of sexual developmental, mitochondrial oxidative phosphorylation disorders, and metabolic disorders (Figure 1a). The germ line of 73 patients with microsatellite stable colorectal cancers was also analyzed. Finally, 119 patients with complex phenotypes were included (Supplementary Table S1 online). The exome sequencing data for all samples were previously analyzed for (potential) pathogenic small variants (mutations) that were found within a corresponding panel of disease genes as previously described.13 (link) In addition, the majority of the neurodevelopmental disorders samples had previously screened negative for CNVs, based mostly on Affymetrix 250k microarray data using an average resolution of 100 kb for deletions and 150 kb for duplications. CNV analysis was performed for all exome samples. First, it was performed for CNVs overlapping genes associated with the genetic-disorder category. Second, exome-wide analysis with a resolution of 200 kb was performed anonymously for all patients.