Samples were prepared following the Nextera® Rapid Capture Exome Enrichment kit protocol and were sequenced on two lanes of a HiSeq 2500 in paired end mode (2 × 100). Reads were aligned with BWA  and variants called with GATK , following the best practice recommendations. Variants were annotated with information from Ensembl , the ExAC project  (allele frequency (AF), variants with AF < 0.01 are called rare), PROVEAN deleteriousness prediction scores (variants with scores < −2.5 are called deleterious)  (for SNPs and indels), and LR.PF3 pathogenicity prediction scores  (for SNPs only). Copy number variations (CNVs) were called with XHMM . MAESTROweb [26, 27] was used to predict the effect of variants on protein stability based on protein structure, where structure data were available. Sequence conservation was computed with ConSurf . A detailed description is given in the Additional file 1.