Mutations in genes encoding ion channel pore-forming α-subunits and accessory 
β-subunits as well as intracellular calcium-handling proteins that collectively 
maintain the electromechanical function of the human heart serve as the 
underlying pathogenic substrate for a spectrum of sudden cardiac death 
(SCD)-predisposing heritable cardiac arrhythmia syndromes, including long QT 
syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and 
catecholaminergic polymorphic ventricular tachycardia (CPVT). Similar to many 
Mendelian disorders, the cardiac "channelopathies" exhibit incomplete 
penetrance, variable expressivity, and phenotypic overlap, whereby 
genotype-positive individuals within the same genetic lineage assume vastly 
different clinical courses as objectively assessed by phenotypic features such 
electrocardiographic abnormalities and number/type of cardiac events. In this 
Review, we summarize the current understanding of the global architecture of 
complex electrocardiographic traits such as the QT interval, focusing on the 
role of common genetic variants in the modulation of ECG parameters in health 
and the environmental and genetic determinants of incomplete penetrance and 
variable expressivity in the heritable cardiac arrhythmia syndromes most likely 
to be encountered in clinical practice.