Inherited Arrhythmia Syndromes and the Variant of Uncertain Significance: Cascade Testing When the Result Is Ambiguous
DOI:
https://doi.org/10.5281/zenodo.22386463Abstract
The inherited arrhythmia syndromes -- long QT syndrome (LQTS), Brugada syndrome, and catecholaminergic
polymorphic ventricular tachycardia (CPVT) among them -- cause sudden cardiac death in people whose hearts are
structurally normal, and a genetic diagnosis in an affected proband is what makes it possible to test relatives before,
rather than after, a life-threatening event [1]. Genetic testing for these conditions has matured from a research tool into
routine clinical practice over the last two decades, guided since 2015 by a shared five-tier framework -- pathogenic, likely
pathogenic, uncertain significance, likely benign, benign -- from the American College of Medical Genetics and Genomics
and the Association for Molecular Pathology (ACMG/AMP) [2].
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