Brugada Syndrome via the CACNA2D1 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
11127 CACNA2D1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11127CACNA2D181479 81479 $890 Order Options and Pricing

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Brugada syndrome (BrS) is a potentially life-threating arrhythmia disorder without structural abnormalities, characterized by dizziness, syncope, nocturnal agonal respiration and sudden death. The classic electrocardiographic findings associated with BrS include ST segment elevation in leads V1 to V3, right bundle branch block, first degree AV block, and intraventricular conduction delay. Brugada syndrome is much more common in men than in women, and many people who have BrS don't have any symptoms. Symptoms usually manifest during adulthood, but they may appear any time between two days and 80 years of age (Antzelevitch et al. 2005). BrS is treatable with preventive measures such as reducing fever, avoiding certain medications and using an implantable cardiac defibrillator (Francis and Antzelevitch 2005).

Genetics

Brugada syndrome is an autosomal dominant disorder with variable expression, resulting from pathogenic variants within genes that encode cardiac ion channels. BrS is also referred to as a “cardiac channelopathy.” Pathogenic variants in 16 genes (CACNA1C, CACNB2, CACNA2D1 , GPD1L , KCND3 , K CNE3 , KCNE5, KC NJ8 , HCN4 , R ANGRF , SCN5A , SCN 1B , SCN2B , SCN3B , SLMAP, an d TRPM4) influencing sodium and calcium currents in the heart are associated with BrS and account for at least 26%-41% of cases of BrS (Kapplinger et al 2010; Crotti et al. 2012). Most patients with BrS have inherited a disease-causing variant from a parent, as de novo mutations in BrS are rare (Hedley et al. 2009).The preproprotein encoded by the CACNA2D1 gene is posttranslationally processed into 2 peptides, an alpha-2 subunit and a delta subunit, which help form voltage-dependent calcium channels. CACNA2D1 genetic variants could reduce L-type calcium channel current, shorten repolarization QT intervals and trigger cardiac arrhythmias (Burashnikov et al. 2010; Bourdin et al. 2015). So far, all pathogenic CACNA2D1 variants reported to cause BrS are missense variants (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the CACNA2D1 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the SCN5A gene cause 15%-30% of Brugada syndrome based on clinical diagnosis. Another ~5% of patients with BrS have pathogenic variants in one of the following genes: GPD1L, CACNA1C, CACNB2, SCN1B, SCN3B, KCNE3, KCNJ8, KCND3, CACNA2D1, MOG1 and HCN4 (Kapplinger et al. 2010; Crotti et al. 2012). Gross deletions or duplications not detectable by sequencing have been reported in CACNA2D1 as individual cases associated with epilepsy and intellectual disability, but not with Brugada Syndrome (Human Gene Mutation Database).

Indications for Test

All patients with symptoms suggestive of Brugada syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
CACNA2D1 114204
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Antzelevitch C. et al. 2005. Circulation. 111: 659-70. PubMed ID: 15655131
  • Bourdin B. et al. 2015. The Journal of Biological Chemistry. 290: 2854-69. PubMed ID: 25527503
  • Burashnikov E. et al. 2010. Heart Rhythm. 7: 1872-82. PubMed ID: 20817017
  • Crotti L. et al. 2012. Journal of the American College of Cardiology. 60: 1410-8. PubMed ID: 22840528
  • Francis J., Antzelevitch C. 2005. International journal of cardiology. 101: 173-8. PubMed ID: 15882659
  • Hedley PL. et al. 2009. Human mutation. 30: 1256-66. PubMed ID: 19606473
  • Human Gene Mutation Database (Bio-base).
  • Kapplinger JD. et al. 2010. Heart rhythm : the official journal of the Heart Rhythm Society. 7: 33-46. PubMed ID: 20129283

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.

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

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ORDER OPTIONS

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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.

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