The conclusion that the increased myofilament calcium sensitivity associated to TNNT2 hot spot mutations is the key trigger for the calcium handling dysregulation that promotes arrhythmias may be limited by the difficulties of relating in vivo patient (and animal) propensity to arrhythmias to in vitro data that measure the propensity to spontaneous activity. The gene discussed is TNNT2; the disease is cardiac arrhythmia.