Arrhythmias & electrophysiology
The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic
Authors' conclusion
In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification.
Study context
- Population
- Patients referred to an inherited arrhythmia clinic who underwent gene panel testing, 2004–2020median age 37 years
- Participants
- 517 patients
- Outcome
- Frequency of variant reclassification (ACMG criteria) and its impact on clinical management
Methodological detailssingle-centre, Variants reinvestigated using ClinVar, VarSome and literature review; reclassified by ACMG criteria
- Single-centre
- Variants reinvestigated using ClinVar, VarSome and literature review; reclassified by ACMG criteria
Main finding
As reported in the abstract
Variant reclassification
- Variant of uncertain significance (VUS) reported
- 94 patients (18.2%)
- VUS more common with large gene panels
- P <.001
- Unique VUSs reclassified
- 28 of 87 (32.2%)
- VUSs reclassified to pathogenic/likely pathogenic
- 11
- VUSs reclassified to benign/likely benign
- 17
- Originally reported pathogenic variants lacking support by ACMG criteria
- 7 of 138 (5.1%)
Observational data: associations, not effects.
Further findings
Association of reclassification with arrhythmic events and management
- Reclassification not associated with arrhythmic events; impacted genotype-specific counseling and future therapeutic options
Original publication
The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic. Heart Rhythm. Published 11 January 2024. doi:10.
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