Why Is This Important?

Knowing if your patient has a hereditary cardiovascular disorder can help you determine their future cardiovascular disease risks and guide your medical management recommendations. Key benefits include:

1. Clarify diagnosis and risk for sudden cardiac arrest 
2. Target medical management and prevention of cardiac arrest and other complications
3. Offer family members genetic testing (for a familial mutation) and implement medical surveillance to only those that need it 
4. Reduce healthcare costs, resources, and anxiety for families

Mutation Detection Rate

CPVTNext will find a mutation in 50-60% of patients with CPVT (clinical sensitivity).  CPVTNext can detect >99.9% of described mutations in the included genes (analytic sensitivity).

Test Description

CPVTNext includes 6 genes associated with CPVT (listed above). These genes are also included in the comprehensive arrhythmia (RhythmNext) and comprehensive cardiovascular genetics (CardioNext) panels. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing¹. This assay targets all coding domains and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis for available genes is performed using a custom pipeline based on read-depth from NGS data and/or utilizing a targeted chromosomal microarray with confirmatory MLPA when applicable.

1. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.