In this study we investigated the genetic cause of ACM in two families using whole exome sequencing. Since all affected and some unaffected individuals were known to harbor PKP2 variants, we investigated whether a second gene was involved in a digenic inheritance pattern, with the second gene either causing ACM in the affected individuals together with PKP2, or compensating the effect of the PKP2 variants in the carriers. We identified 74 and 212 genes in families 1 and 2, respectively, which carried variants consistent with the mode of digenic inheritance. To obtain results that can be easily interpreted, we restricted our analysis to genes either associated with ACM or related to PKP2. In family 1 we identified four genes that are annotated with the same biological process as PKP2. In family 2 we identified the ACM associated gene TTN and ten genes related to PKP2 through a shared biological process or protein interactions (see Fig. 2).