Arrhythmias & electrophysiology
Enhancing the interpretation of genetic observations in KCNQ1 in unselected populations: relevance to secondary findings
Authors' conclusion
Rare missense variants with a clear phenotype of LQTS have a high likelihood to be present within the pore and adjacent TM segments (S5-Pore-S6) and a greater tendency to be present within CR2.
Study context
- Population
- Carriers of rare KCNQ1 (Kv7.1) missense variants; relevance to secondary findings in whole exome sequencing
- Comparison
- KCNQ1 rare variants in patients with diagnosed or suspected LQTS vs an unselected population
- LQTSn = over 3,700
- Unselected populationn = 140,000reference
- Outcome
- Domain-specific enrichment of KCNQ1 missense variants associated with LQTS
Main finding
As reported in the abstract
LQTS-associated KCNQ1 variant enrichment by channel region
Significant enrichment in 3 regions: pore, S5 and S6 transmembrane (TM) regions
OR >2
Observational data: associations, not effects.
Further findings
Variant enrichment in carboxyl-terminus conserved region 2 (CR2)
- Increased OR of disease association
Cardiac events by S5-Pore-S6 variant location
- S5-Pore-S6 region correlated with a significant increase in cardiac events
Original publication
Enhancing the interpretation of genetic observations in KCNQ1 in unselected populations: relevance to secondary findings. Europace. Published 28 October 2023. doi:10.
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