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BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary arrhythmia disorder characterized by syncope or sudden cardiac death and typically caused by a gain-of-function of the Ryanodine Receptor Type 2 (RyR2) mutation. Calmodulin is a calcium-binding protein responsible for many intracellular signalling pathways and disruptions in function or regulation may lead to potentially fatal arrhythmias. We present a case of a young patient with CPVT found to have an unusual, potentially causative, Calmodulin 2-a protein coding gene (CALM2) mutation. CASE SUMMARY: A 21-year-old female with autism was brought to the ED following cardiac arrest. Bidirectional ventricular tachycardia was captured on electrocardiogram. Propranolol was initiated, and patient had no further episodes of ventricular arrhythmia. A subcutaneous implantable cardioverter defibrillator (ICD) was implanted, and further genetics testing was done. Rapid Whole Genome Sequencing (PGnome®-RAPID) resulted heterozygous variant of uncertain significance in CALM2 gene NM_001743.5 for variant c.136G>A. DISCUSSION: To the authors knowledge, this is the third known record of such mutation in accordance with the International Calmodulin Registry (n = 74). Identification of CALM mutations can help advance the understanding of genetic underpinnings of arrhythmias and underscore necessity of genetic screening and personalized treatment strategies. Subcutaneous ICDs offer a promising therapeutic option while minimizing risks associated with traditional transvenous ICDs.

Pathogenic and likely pathogenic variants in the TECRL gene are known to be associated with recessive catecholaminergic polymorphic ventricular tachycardia 3, which can include prolonged QT intervals (MIM#614021). We report a case of cardiac arrest in a previously healthy adolescent male in the community. The patient was found to have a novel maternally inherited likely pathogenic variant in TECRL (c.915T>G [p.Tyr305Ter]) and an additional 19-kb duplication encompassing multiple exons of TECRL (chr4:65165944-65185287, dup [4q13.1]) not identified in the mother. Genetic results were revealed via rapid whole-genome sequencing, which allowed appropriate treatment and prognostication.