Heart failure & cardiomyopathiesCohort study
RBM20 Truncating Variants and Human Cardiomyopathy
- Cohort study
- genome-first biobanks (UK Biobank, All of Us)
- retrospective international registry
Authors' conclusion
This study found that RBM20 variants contributed to arrhythmogenic DCM phenotypes but conferred reduced lifetime disease penetrance compared to TTNtvs and milder disease severity alone than P/LP RBM20 variants.
Study context
- Population
- Participants in UK Biobank and All of Us, and patients with dilated cardiomyopathy (DCM) and RBM20 variants at international centres of excellence for genetic heart diseaseUK Biobank (UKB) 4249
- Exposure
- RBM20 truncating variants vs P/LP RBM20 variants, VUS in RBM20 and TTNtvs
- Outcome
- Major ventricular arrhythmias, end-stage HF and HF hospitalization
Main finding
As reported in the abstract
Hazard ratio (95% CI)P value
RBM20 variants vs TTNtvslifetime incidence of cardiomyopathy, HF or major ventricular arrhythmia, genome-first biobanks
0.55(0.36–0.84)
P < 0.001RBM20tvs vs P/LP RBM20sex-adjusted lifetime hazard, patients with DCM
0.13(0.03–0.56)
P = 0.01Observational data: associations, not effects.
Further findings
| Outcome | RBM20tvs | P/LP RBM20 | TTNtvs | P value |
|---|---|---|---|---|
| Age at presentation to referral centres (DCM) | mean 53 (SD 10) years | mean 34 (SD 18) years | Not reported in the abstract | P < 0.001 |
| Family history of sudden cardiac arrest (DCM) · 2 of 10 vs 11 of 17 | 20% | 65% | Not reported in the abstract | P = 0.046 |
| Family history of cardiomyopathy (DCM) · 2 of 10 vs 14 of 18 | 20% | 78% | Not reported in the abstract | P < 0.001 |
Etiologic fraction of RBM20 variants in arrhythmogenic DCM
- Etiologic fraction
- 0.53 (95% CI, 0.32-0.67; P < .001)
Original publication
RBM20 Truncating Variants and Human Cardiomyopathy. JAMA Cardiol. Published 1 May 2026. doi:10.1001/jamacardio.2026.0401
Summarised from the published abstract; every number is checked against it