Exome library preparation, sequencing, and bioinformatics were performed as previously described.15 (link) Briefly, samples were prepared using either the SureSelect Target Enrichment System (Agilent Technologies, Santa Clara, CA), SeqCap EZ VCRome 2.0 (Roche NimbleGen, Massion, WI),16 (link) or the IDT xGen Exome Research Panel V1.0 (Integrated DNA Technologies, Coralville, IA) and sequenced using paired-end, 100- or 150-cycle chemistry on the Illumina HiSeq or NextSeq (Illumina, San Diego, CA). Stepwise filtering included the removal of common single-nucleotide polymorphisms, intergenic and 3′/5′ untranslated region variants, intronic variants outside ±2, and synonymous variants (other than potential splice-related synonymous changes at the first and last positions of exons). However, alterations classified as pathogenic or likely pathogenic based on Ambry's variant classification schema as well as alterations with a Human Gene Mutation Database identifier were protected from the aforementioned filtering. Identified candidate alterations were confirmed using automated fluorescence dideoxy sequencing.