Arrhythmias & electrophysiology
Standing genetic variation affects phenotypic heterogeneity in an SCN5A-mutation founder population with excess sudden cardiac death
Authors' conclusion
Our data suggest that other variants, alongside a pathogenic mutation, are associated with phenotypic heterogeneity.
Study context
- Population
- Multigeneration founder pedigree (Worm Study) segregating SCN5A p.(Phe1617del), with excess sudden cardiac deathgenotyped at linkage peak
- Participants
- 70 participants
- Outcome
- Association of chromosome 3 locus variants (minor allele frequency >0.10) with cardiac conduction disease and isorhythmic dissociation
Methodological detailsfamily-aware phasing, founder population
- Family-aware phasing
- Founder population
Main finding
As reported in the abstract
- Homozygous SCN10A missense variant (rs12632942) associated with isorhythmic dissociation after multiple-comparison correction: OR 11.23 (95% CI 2.76-23.39)
- P = 1.2 × 10-4
Further findings
Haplotype structure
- Haplotypes carrying p.Phe1617del deletion
- 1
- Estimated age of deletion (generations)
- ∼18
- Other missense variants on carrier haplotype spanning SCN5A/SCN10A/SCN11A
- 5
- Noncarrier haplotypes
- 74
- Noncarrier haplotype frequency range
- 0.5% to 5%
Original publication
Standing genetic variation affects phenotypic heterogeneity in an SCN5A-mutation founder population with excess sudden cardiac death. Heart Rhythm. Published 9 February 2023. doi:10.
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