The genetic basis of dilated cardiomyopathy (DCM) is recognized but still not widely utilized in diagnostics. Hundreds of mutations in coding exons of over 50 genes have been reported to associate with isolated DCM. We applied oligonucleotide-selective sequencing and custom data analysis and interpretation pipelines to identify pathogenic base substitutions and insertions and deletions in 101 genes associated with cardiomyopathies. Our sequencing panel covered coding exons, exon-intron boundaries and known variants in intronic regions of target genes. We genetically profiled 147 well-characterized DCM patients with average clinical follow-up of 8.7 years. On average, 99.1% of the targeted regions were covered >15x. We identified pathogenic or likely pathogenic variants in 50% of the familial and 27% of the sporadic cases. These included truncating TTN mutations affecting all transcripts that were identified in 21% of the familial and 13% of the sporadic cases. Family segregation analysis revealed that all tested truncating TTN mutations co-segregated with the DCM disease. We observed a trend of less atrial fibrillation, conduction abnormalities and pacemaker/ICD/CRT related therapies in patients with TTN mutations compared to patients with other mutations or patients without identified mutations. Other major findings in the analysis were mutations in genes encoding the nuclear lamina, the desmosome and the sarcomere. Mutation positive DCM patients and especially those with a LMNA mutation had significantly more atrial fibrillation when compared to mutation negative individuals. In conclusion, our analysis revealed high diagnostic yield in the familial form of DCM. It further confirms that truncating TTN mutations are a significant contributor to familial DCM. Authors disclosure: None: OA, LO, HK, MK, TO and TH. Minor: JT, MG, SM*, TPA* and JWK*. *Founders of Blueprint Genetics, which offers gene diagnostics for cardiomyopathies.