A SCN5A gene mutation (c.1768 A>C, p.K590Q) in a patient with Brugada syndrome: a case report

Brugada syndrome (BrS) is an arrhythmia disorder most commonly associated with loss-of-function variants in the SCN5A gene. We report a 33-year-old man presenting with spontaneous type-1 BrS electrocardiographic (ECG) pattern and recurrent syncope.

Sequencing revealed a heterozygous SCN5A variant, c.1768 A>C (p.K590Q), which was absent from the Human Gene Mutation Database (HGMD), gnomAD (allele frequency 0.000004), ClinVar, and the 1000 Genomes database. The substituted lysine is highly conserved across species (HomoloGene) and resides in the domain II-III linker at the extracellular pore entrance. In silico analyses (PolyPhen-2 and MutationTaster) predicted a deleterious effect. Following implantation of an implantable cardioverter-defibrillator, the patient has remained asymptomatic for 14 months. The same variant was detected in his 6-year-old son, who currently shows no ECG abnormalities.

The SCN5A c.1768 A>C substitution represents a novel, ultra-rare missense change variant. Its evolutionary conservation, predicted pathogenicity, and familial segregation support a probable association with BrS, warranting further functional characterization.