Figure 4. Distribution of QTc duration in health and in long QT syndrome.

Continuous line represents QTc distribution in health. Dashed line represents QTc distribution in long QT syndrome. The circles display the genetic architecture of the QTc duration consisting of very rare variants with <1% minor allele frequency (MAF) but large effect on the QTc duration, common rare variants with 1–5% MAF with an intermediate effect on QTc duration, and common variants with >5% MAF but small effect on the QTc duration. Rare variants are mutations that are traditionally linked to the long QT syndrome; however, they may be found in persons with normal QTc duration. Common variants are expected to minimally influence (prolong or shorten) the QTc duration. Common rare include variants associated with strong modifying effects on the QTc duration in the general population and variants associated with LQTS only in the co-presence of a non-genetic trigger (a ‘second hit’).