Associated disorders

The SCN5A gene is associated with autosomal dominant Brugada syndrome (BrS) (MedGen UID: 468523), long QT syndrome (LQTS) type 3 (MedGen UID: 349087), dilated cardiomyopathy (DCM) (MedGen UID: 331341), and atrial fibrillation (MedGen UID: 462814). Other SCN5A-related conditions have been reported (OMIM: 600163).

Pathogenic SCN5A variants cause 15%-30% of cases of BrS and 5% of cases of LQTS. Pathogenic SCN5A variants are a rare cause of DCM and are associated with an unknown percentage of atrial fibrillation.

Voltage-gated sodium channels allow sodium ions into the cell after the application of a current, as in the case of neuron firing (depolarization). The SCN5A gene encodes an alpha subunit of a voltage-gated sodium channel expressed primarily in the heart, and it is required for regulating depolarization and re-establishing resting membrane potential.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
SCN5A NM_198056.2