Key result
Novel p.1449Y>H SCN5A loss-of-function variant presents with complete LBBB masking typical Brugada syndrome ECG findings.
Why the study?
SCN5A variants are associated with Brugada syndrome and conduction disturbances, where patch-clamp functional assessment aids pathogenic classification and evaluates disease penetrance and severity.
Observational
Highlights that complete left bundle branch block can mask typical Brugada syndrome ECG findings in patients with the novel p.1449Y>H SCN5A loss-of-function variant.
Answers are grounded in this paper and cite their sources.
Functional SCN5A assessment aids variant classification in overlap phenotypes; leaves open penetrance estimates for clinical use.
SCN5A gene variants are associated with both Brugada syndrome and conduction disturbances, sometimes expressing an overlapping phenotype. Functional consequences of SCN5A variants assessed by patch-clamp electrophysiology are particularly beneficial for correct pathogenic classification and are related to disease penetrance and severity. Here, we identify a novel SCN5A loss of function variant, p.1449Y>H, which presented with high penetrance and complete left bundle branch block, totally masking the typical findings on the electrocardiogram. We highlight the possibility of this overlap combination that makes impossible an electrocardiographic diagnosis and, through a functional analysis, associate the p.1449Y>H variant to SCN5A pathogenicity.
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Arana‐Rueda et al. (2021) conducted an observational in Brugada syndrome and complete left bundle branch block. p.1449Y>H SCN5A variant was evaluated on Pathogenicity and functional consequences of the p.1449Y>H SCN5A variant. The novel p.1449Y>H SCN5A loss of function variant presented with high penetrance and complete left bundle branch block, completely masking typical Brugada syndrome electrocardiogram findings.
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