Comprehensive Genomic Analysis of Dilated Cardiomyopathy

See Supplementary Methods for expanded sequencing methods. Briefly, 42 patient DNA samples were newly sequenced by WGS, or previously sequenced using a custom capture panel for 67 or 69 DCM genes.¹² WES data were generated in-house from the NA12878 cell line (Coriell Institute for Medical Research, Camden, NJ) using the SureSelect^XT Human AllExon V5 ([SSv5], Agilent Technologies, Santa Clara, CA, n=1) and the Clinical Research Exome V2 ([CREv2], Agilent, n=13) capture kits. We also re-analyzed published data from samples that used SureSelect^XT Human AllExon V6 ([SSv6], Agilent, n=6) capture kit.^{13 (link)} All genomic data, including previously published data, were analyzed using a GATK best practices analysis pipeline.^{14 (link)} Short variants were annotated, filtered and prioritized using Seave.^{15 (link)} Structural variants (SV) including copy number variants were identified using ClinSV (Minoche et al, manuscript in preparation) which uses a combination of discordantly mapping read pairs, split-mapping reads, and depth of coverage changes. A genomic position was defined as “covered” if the sequencing depth had ≥15 high quality reads.^{16 (link)} Selected variants were confirmed in probands and evaluated in family members using Sanger sequencing and/or PCR.