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Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome via the CALM1 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
3963 CALM1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3963CALM181479 81479,81479 $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.

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

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited arrhythmogenic heart disorder characterized by life-threatening electrical instability induced by physical or emotional stress without any structural cardiac abnormalities (Napolitano et al. 2014). 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.

Long QT syndrome (LQTS) is a heritable channelopathy characterized by a prolonged cardiac repolarization that may trigger ventricular arrhythmias (torsade de pointes), recurrent syncopes, seizure, or sudden cardiac death (SCD) (Cerrone et al. 2012). LQTS can manifest with syncope and cardiac arrest that is commonly triggered by adrenergic stress, often precipitated by emotion or exercise. Roughly 10% to 15% of patients experience symptoms at rest or during the night (Schwartz et al. 2001). The mean age of onset of symptoms is 12 years, and earlier onset usually is associated with a more severe form of the disease (Priori et al 2004).

Genetics

Pathogenic variants in CALM1 can cause multiple disorders, such as Long QT syndrome type 14 (LQT14) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Both are inherited in an autosomal dominant manner. CALM1 encodes a 149 amino acid protein, spans around 10 kb and is located at Chr 14p32.11 (Berchtold et al. 1993). CALM1 is the archetype of the calmodulin (calcium-modulated proteins) family of which nearly 20 members have been identified. Calmodulin (CaM) is a multifunctional calcium ion sensor protein that transduces much of the calcium signaling (Kobayashi et al. 2015). Pathogenic variants in CALM1 impair calcium binding of calmodulin and disturb calmodulin-RYR2 interaction, which plays a key role in arrhythmia and heart failure (Nyegaard et al. 2012; Xu et al. 2010). So far, all pathogenic variants reported in CALM2 are missense (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

CALM1 pathogenic variants contribute less than 1% of Catecholaminergic Polymorphic Ventricular Tachycardia (Nyegaard et al. 2012). Up to 70% of patients with a clinical diagnosis of Long QT syndrome have identifiable pathogenic variants (Beckmann et al. 2013). The majority of LQTS cases are caused by pathogenic variants in one of three genes: KCNQ1, KCNH2 and SCN5A. Approximately 5% of LQTS pathogenic variants are contributed together by: ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5, CALM1 and CALM2 (Lieve et al. 2013; Kapplinger et al. 2009; GeneReviews 2015).

To date, no gross deletions or duplications have been reported in CALM1 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the CALM1 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 Long QT and Catecholaminergic Polymorphic Ventricular Tachycardia syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
CALM1 114180
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Catecholaminergic Polymorphic Ventricular Tachycardia Panel
Comprehensive Cardiac Arrhythmia Panel
Comprehensive Cardiology Panel
Sudden Cardiac Arrest Panel

Citations

  • Alders M., Christiaans I. Long QT Syndrome. 2015. 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: 20301308
  • Berchtold M.W. et al. 1993. Genomics. 16:461-5. PubMed ID: 8314583
  • Cerrone M. et al. 2012. Circulation. Cardiovascular genetics. 5: 581-90. PubMed ID: 23074337
  • Human Gene Mutation Database (HGMD).
  • Kobayashi H. et al. 2015. Development. 142: 375-84. PubMed ID: 25519244
  • Napolitano C. et al. 2014. Catecholaminergic Polymorphic Ventricular Tachycardia. 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: 20301466
  • Nyegaard M. et al. 2012. American Journal of Human Genetics. 91: 703-12. PubMed ID: 23040497
  • Priori S.G. et al. 2004. JAMA. 292: 1341-4. PubMed ID: 15367556
  • Schwartz P.J. et al. 2001. Circulation. 103: 89-95. PubMed ID: 11136691
  • Xu X. et al. 2010. Biochemical and Biophysical Research Communications. 394: 660-6. PubMed ID: 20226167

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.
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