Catecholaminergic Polymorphic Ventricular Tachycardia via the RYR2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11633 RYR2 81408 81408,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11633RYR281408 81408(x1), 81479(x1) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic heart disorder characterized by life-threatening electrical instability induced by physical or emotion stress without any structural cardiac abnormalities (Napolitano et al. GeneReviews, 2009). The electrical instability may degenerate into cardiac arrest and sudden death. CPVT typically onsets during childhood and often presents as syncope. Preventative drugs (beta-blockers) and other treatments are available for susceptible individuals.

Genetics

CPVT due to RYR2 variants is inherited in an autosomal dominant manner. The large RYR2 (ryanodine receptor type 2) gene with 105 exons encodes the cardiac muscle calcium release channel. RYR2 pathogenic variants are almost entirely missense and are clustered in specific portions of the gene (eg Priori et al. Circulation 106:69-74, 2002; Medeiros-Domingo et al. J Am Coll Cardiol 54:2065-2074, 2009). In-frame deletions or insertions of one or two amino acids have also been reported. A few patients had a deletion of the entire exon 3 (in-frame loss of 35 amino acids) (Marjamaa et al. BMC Med Genet 10:12, 2009). The penetrance of RYR2 causative variants is high, but not 100% (Napolitano et al. GeneReviews, 2012). Some patients have been reported to carry de novo variants (Roux-Buisson et al. Europace 13:130-132, 2010). CPVT can also be caused by recessive variants in the CASQ2 gene (diBarletta et al. Circulation 114:1012-1019, 2006). In addition to CPVT, dominant variants in RYR2 have been reported to be a rare cause of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (McNally et al. GeneReviews, 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Priori et al. (Circulation 106:69-74, 2002) reported that about 50% of CPVT patients have variants in the RYR2 gene. Tester et al. (Mayo Clin Proc 79:1380-1384, 2004) reported that 14% of sudden unexplained death cases had RYR2 variants. CASQ2 variants are reported in only 1-2% of CPVT patients (Napolitano et al. GeneReviews, 2009).

Testing Strategy

This test provides full coverage of all coding exons of the RYR2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

All individuals diagnosed with CPVT are candidates for this test. Individuals with exercise or stress induced cardiac arrest or sudden unexplained death are also candidates. When dealing with affected families, PreventionGenetics recommends that gene testing be performed first on a clearly affected family member. If a likely causative variant is found in the affected individual, then other family members can be tested at a much reduced cost.

Gene

Official Gene Symbol OMIM ID
RYR2 180902
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • di Barletta, M. R. et.al. (2006). "Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia." Circulation 114(10): 1012-1019. PubMed ID: 16908766
  • Marjamaa A et al. 2009. Bmc Medical Genetics. 10: 12. PubMed ID: 19216760
  • McNally E. et al. 2014. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301310
  • Medeiros-Domingo A. et al. 2009. Journal of the American College of Cardiology. 54: 2065-74. PubMed ID: 19926015
  • Napolitano C, Priori SG, Bloise R. Catecholaminergic Polymorphic Ventricular Tachycardia. 2004 Oct 14 [Updated 2012 Feb 16]. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. PubMed ID: 20301466
  • Priori SG. et al. 2002. Circulation. 106: 69-74. PubMed ID: 12093772
  • Roux-Buisson, N., et.al. (2010). PubMed ID: 20851825
  • Tester, D. J., et.al. (2004). PubMed ID: 15544015

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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