POPDC2 and cardiac rhythm disease: (1) The cardiac arrhythmia phenotype of the affected individuals harboring these variants in the homozygous or compound heterozygous state is similar to observations of sinus pauses and bradycardia that were made in mice lacking Popdc25 and to AV block observed in zebrafish after morpholino knockdown of popdc2. 6(2) The variants affect highly conserved residues and are predicted damaging by multiple in silico prediction tools.