(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. The gene discussed is POPDC2; the disease is cardiac arrhythmia.