Recognizing such conditions in the initial stages is key, given the better response to treatment of Fabry patients when enzyme replacement therapy is started earlier,28 and given that sudden cardiac death is a frequent cause of death in Danon disease.29 Through the newly devised metric DEff, we suggest that PLN should be treated as a “core”—although rare—HCM gene, whereas for ACTN2 and MYOZ2 only specific screens for plausibly pathogenic variants would be effective. The gene discussed is ACTN2; the disease is Danon disease.