This test is for individuals with a clinical diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). The Invitae Catecholaminergic Polymorphic Ventricular Tachycardia Panel analyzes eight genes that are definitively associated with CPVT or other inherited arrhythmia disorders that can present with clinical features similar to CPVT.
Individuals with clinical symptoms of CPVT may benefit from diagnostic genetic testing to establish or confirm diagnosis, clarify risks, or inform management. Asymptomatic members of a family with a known pathogenic variant may also benefit by avoiding activities that can trigger symptoms.
ANK2 CALM1 CALM2 CALM3 CASQ2 KCNJ2 RYR2 TRDN
ANK2 CALM1 CALM2 CALM3 CASQ2 KCNJ2 RYR2 TRDN
CPVT syndrome can also be ordered as part of broader panels to test for arrhythmia disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary arrhythmia that can cause syncope (fainting) and sudden cardiac arrest. Symptoms are caused by a fast ventricular arrhythmia that may terminate spontaneously or turn into ventricular fibrillation.
Episodes of arrhythmia frequently occur during exercise or acute emotional stress. The electrocardiogram (ECG) is usually normal at rest, and a stress test is typically used to identify ventricular arrhythmia during exercise.
This test covers all the common genetic causes of CPVT. Analysis of the genes on this panel is expected to uncover a pathogenic variant in up to 65% of clinical cases of CPVT. Approximately 50%-60% of individuals with a clinical diagnosis of CPVT have a pathogenic variant in the RYR2 gene. An additional 3%-5% of individuals are found to have two pathogenic variants in the CASQ2 gene. The remaining genes in this test account for an unknown percentage of CPVT cases.
CPVT is most commonly inherited in an autosomal dominant pattern. However, as many as 40% of cases occur because of spontaneous de novo variants in the RYR2 gene. CASQ2-related CPVT and TDRN-related CPVT are autosomal recessive.
CPVT exhibits reduced penetrance, meaning that not everyone who inherits a predisposition to develop CPVT will go on to manifest the disorder. The age of onset varies, but symptoms frequently present in childhood between ages 7 and 12 years. When untreated, up to 80% of individuals will experience syncope in their lifetimes and an estimated 30% will experience sudden cardiac arrest.
The prevalence of CPVT is not well established but is an estimated 1 in 10,000 individuals.
This test may be considered for individuals with:
For links to published management guidelines for cardiology conditions, please refer to our Management guidelines page.
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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|