ALPK3 and heart failure: This HCM case presents compound heterozygosity for an ALPK3 nonsense mutation (c.4234C > T) coupled with a missense mutation (c.3491G > A), compared to ALPK3 heterozygotes, compound heterozygous carriers exhibit an aggressive clinical profile characterized by the following: (1) early disease onset, (2) biventricular hypertrophy with multilevel obstruction, (3) an elevated risk of sudden cardiac death, and (4) accelerated heart failure progression.