Table 6.
Genes implicated in long QT syndrome (LQTS)
| Gene | Locus | Phenotype—syndrome | Protein (functional effect) | Frequency | ClinGen classification |
|---|---|---|---|---|---|
| KCNQ1 | 11p15.5 | LQTS, JLNS | Loss-of-IKs channel function | 40–55% | Definitive |
| KCNH2 | 7q35-36 | LQTS | Loss-of-IKr channel function | 30–45% | Definitive |
| SCN5A | 3p21-p24 | LQTS | Increase in INa1.5 channel function | 5–10% | Definitive |
| CALM1 | 14q32.11 | LQTS | L-type calcium channel (↑) | <1% | Definitive |
| CALM2 | 2p21 | LQTS | L-type calcium channel (↑) | <1% | Definitive |
| CALM3 | 19q13.32 | LQTS | L-type calcium channel (↑) | <1% | Definitive |
| TRDN | 6q22.31 | Recessive LQTS | L-type calcium channel (↑) | <1% | Strong |
| KCNE1 | 21q22.1 | LQTS, JLNS, a-LQTS | Loss-of-IK channel function | <1% | Strong in aLQTS, definitive in JLNS |
| KCNE2 | 21q22.1 | a-LQTS | Loss-of-IK channel function | <1% | Strong in aLQTS |
| KCNJ2 | 17q23 | ATS | Loss-of-IK1 channel function | <1% | Definitive in ATS |
| CACNA1C | 12p13.3 | TS, LQTS | L-type calcium channel (↑) | <1% | Definitive in TS, moderate in LQTS |
Functional effect: (↓) loss-of-function or (↑) gain-of-function at the cellular in vitro level.
a-LQTS, acquired-long QT syndrome; ATS, Andersen–Tawil syndrome; JLNS, Jervell and Lange-Nielsen syndrome; RWS, Romano–Ward syndrome; TS, Timothy syndrome.