Associated disorders

The PKP2 gene is associated with autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) (MedGen UID: 373205), Brugada syndrome (PMID: 24352520) and dilated cardiomyopathy (DCM) (PMID: 20716751).

Pathogenic PKP2 variants are associated with 10%-52% of clinical cases of ARVC and an unknown percentage of cases of BrS.

The PKP2 gene encodes the protein plakophilin-2. This protein is part of the desmosome complex, which is present in both muscle and skin cells. The primary role of the desmosome is to adhere cells to each other, thus maintaining the structural integrity of skin and muscle tissues. Pathogenic variants in genes encoding cardiac-specific desmosome proteins are a common cause of arrhythmogenic right ventricular cardiomyopathy.

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
PKP2 NM_004572.3