DNA icon

Long QT Syndrome via the CALM2 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
11133 CALM2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11133CALM281479 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

Long QT syndrome (LQTS) is a heritable channelopathy characterized by an exceedingly prolonged cardiac repolarization that may trigger ventricular arrhythmias (torsade de pointes), recurrent syncope, seizure, or sudden cardiac death (SCD) (Cerrone et al. 2012). The incidence of LQTS has been estimated between 1 in 2500 and 1 in 7000 in the general population. 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). Inherited LQTS occurs due to pathogenic variants in multiple genes such as KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), ANK2 (LQT4), KCNE1 (LQT5), KCNE2 (LQT6), KCNJ2 (LQT7), CACNA1C (LQT8), CAV3 (LQT9), SCN4B (LQT10), AKAP9 (LQT11), SNTA1 (LQT12) and KCNJ5 (LQT13), CALM1 (LQT14) and CALM2 (LQT15), but it can also be acquired, usually as a result of pharmacological therapy. A small percentage of cases of LQTS occur in people who have an underlying variation in the CALM2 gene.

Genetics

Long QT syndrome type 15 (LQT15) is caused by pathogenic variants in CALM2 and is inherited in an autosomal dominant manner. CALM2 encodes a 149 amino acid protein, spans 16 kb and is located at Chr 2p21 (Toutenhoofd et al. 1998; Crotti et al. 2013). CALM2 is a member of the calmodulin gene family. Calmodulin is a calcium binding protein and functions as a Ca2+ sensor in a wide range of intracellular Ca2+-signaling pathways. Causative variants in CALM2 significantly reduce Ca2+ affinity in the C-domain and disrupt the ability of cell to transduce intracellular Ca2+ signals leading to cardiac arrhythmia susceptibility (Makita et al. 2014). So far, all pathogenic variants reported in CALM2 are missense (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

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).

Testing Strategy

This test provides full coverage of all coding exons of the CALM2 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 syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
CALM2 114182
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Long QT Syndrome 15 AD 616249

Citations

  • Beckmann B.M. et al. 2013. European Journal of Human Genetics. 21: N/A. PubMed ID: 23511927
  • Cerrone M. et al. 2012. Circulation. Cardiovascular genetics. 5: 581-90. PubMed ID: 23074337
  • Crotti L. et al. 2013. Circulation. 127: 1009-17. PubMed ID: 23388215
  • Human Gene Mutation Database (Bio-base).
  • Kapplinger J.D. et al. 2009. Heart Rhythm. 6: 1297-303. PubMed ID: 19716085
  • Lieve K.V. et al. 2013. Genetic Testing and Molecular Biomarkers. 17: 553-61. PubMed ID: 23631430
  • Makita N. et al. 2014. Circulation. Cardiovascular Genetics. 7: 466-74. PubMed ID: 24917665
  • 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
  • Toutenhoofd S.L. et al. 1998. Cell Calcium. 23: 323-38. PubMed ID: 9681195

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×