Key result
Low-penetrant p.R190Q KCNQ1 variant requires a second hit to trigger QTc prolongation.
Why the study?
Does the heterozygous p.R190Q KCNQ1 variant require a second hit to cause QTc prolongation and arrhythmia risk in long QT syndrome?
Case Report (n=1)
Does the heterozygous p.R190Q KCNQ1 variant require a second hit to cause QTc prolongation and arrhythmia risk in long QT syndrome?
The high-risk p.R190Q KCNQ1 variant in LQTS exhibits low penetrance on its own and requires a second genetic or acquired hit to manifest QTc prolongation.
Answers are grounded in this paper and cite their sources.
Low-penetrant LQTS phenotype with isolated p.R190Q KCNQ1; hypothesis-generating for modifier variants or acquired QTc factors in case reports.
The heterozygous missense p.R190Q KCNQ1 mutation represents one of the most frequent high-risk variants in long QT syndrome (LQTS). However, the presented case report and the data in literature led us to conclude that this heterozygous variant alone is associated with a low-penetrant clinical and electrocardiographical phenotype, while its co-inheritance with either the heterozygous p.E1053K SCN5A variant, some other LQTS-associated/modifying variant, or with some acquired QTc-inducing condition (like a specific leukaemia medication), may trigger QTc prolongation and thus a risk for arrhytmias.
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Karabinoš et al. (2025) conducted a case report in Long QT syndrome (LQTS) (n=1). Heterozygous missense p.R190Q KCNQ1 mutation was evaluated on QTc prolongation and risk for arrhythmias. The heterozygous p.R190Q KCNQ1 variant alone is associated with a low-penetrant phenotype, requiring a second hit such as another variant or QTc-inducing condition to trigger QTc prolongation.
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