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Timothy Syndrome and Brugada Syndrome via the CACNA1C 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
11123 CACNA1C 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11123CACNA1C81479 81479(x2) $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

  • Chun-An Chen, PhD

Clinical Features and Genetics

Clinical Features

Timothy syndrome is characterized by physical malformations, neurological and developmental defects, including syndactyly, heart QT-prolongation and arrhythmias, developmental delay and autism spectrum disorders. Timothy syndrome is also called Long QT syndrome with syndactyly or long QT syndrome (LQT8) (Krause et al. 2011). Two forms of Timothy syndrome have been described: the classic type (type 1) and a second form caused by mutations in an alternatively spliced form (type 2). Type 1 includes all of the characteristic features described above. Type 2, or the atypical type, causes a more severe form of long QT syndrome and a greater risk of arrhythmia and sudden death. Unlike the classic type, the atypical type does not appear to cause webbing of the fingers or toes.

Brugada syndrome (BrS) is a potentially life-threating rhythm disorder characterized by ST segment elevation on ECG. Other findings may include right bundle branch block, first degree AV block, and intraventricular conduction delay. Brugada syndrome is treatable with preventive measures such as reducing fever, avoiding certain medications and using implantable cardiac defibrillator (Francis and Antzelevitch 2005).

Genetics

CACNA1C-related Timothy and Brugada syndrome are inherited in an autosomal dominant manner. The majority of causative mutations in CACNA1C are missense mutations. CACNA1C encodes the Alpha-1C subunit of the cardiac L-type calcium channel which is important for excitation and contraction of the heart. Mutations in CACNA1C are responsible for all reported cases of Timothy syndrome. Most cases of Timothy syndrome are not inherited from an affected parent, but occur for the first time in a family due to a spontaneous de novo change in the CACNA1C gene (Splawski et al. 2005). Mutations in at least 7 genes (CACNA1C, CACNB2, GPD1L, KCNE3, SCN1B, SCN3B and SCN5A) influencing sodium and calcium currents in the heart are associated with BrS and account for at least 26%-41% of cases of Brugada syndrome. Most patients with Brugada syndrome have inherited a disease-causing mutation from a parent as de novo mutations in BrS are rare (Hedley et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing analysis should yield positive results for nearly 100% of individuals with Timothy syndrome type 1 (Splawski et al 2004). The detection rates for Timothy syndrome type 2 and Brugada syndrome via CACNA1C cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because all mutations reported are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the CACNA1C 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 patients with symptoms suggestive of Brugada syndrome and Timothy syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
CACNA1C 114205
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Brugada Syndrome 3 611875
Timothy Syndrome AD 601005

Citations

  • 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).
  • Krause U, Gravenhorst V, Kriebel T, Ruschewski W, Paul T. 2011. A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). Clin Res Cardiol 100: 1123–1127. PubMed ID: 21915623
  • Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. 2005. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc. Natl. Acad. Sci. U.S.A. 102: 8089–8096; discussion 8086–8088. PubMed ID: 15863612
  • Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT. 2004. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119: 19–31. PubMed ID: 15454078

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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