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Long QT Syndrome and Jervell and Lange-Nielsen syndrome via the KCNQ1 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
11421 KCNQ1 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11421KCNQ181406 81406(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

  • 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 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). Inherited LQTS occurs due to mutations in multiple genes such as KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5) and KCNE2 (LQT6), but it can also be acquired (acquired LQTS), usually as a result of pharmacological therapy. A small percentage of cases of acquired LQTS occur in people who have an underlying variation in the KCNQ1 gene.

Genetics

LQT1 accounts for about 42% of all long QT syndrome cases and occurs due to heterozygous mutations in the KCNQ1 (KvLQT1) gene (Splawski et al. 2000), suggesting an autosomal dominant mode of inheritance. Female predominance has often been observed and has sometimes been attributed to an increased susceptibility to cardiac arrhythmias in women (Imboden et al. 2006). Causative mutations in KCNQ1 include missense, nonsense, splicing and regulatory variants as well as small deletions and insertions. Most mutations reside in intracellular (52%) and transmembrane (30%) domains; 12% are found in pore and 6% in extracellular segments (Splawski et al. 2000).

KCNQ1 codes for the voltage-gated potassium channel protein KvLQT1 that is highly expressed in the heart muscle and inner ear, and helps transport positively charged potassium ions out of cells. In the heart, the channels are involved in recharging the cardiac muscle after each heartbeat to maintain a regular rhythm. In the inner ear, these channels help maintain the proper ion balance needed for normal hearing. The KCNQ1 protein is also produced in the kidney, lung, stomach, and intestine, where it is involved in transporting molecules across cell membranes.

Mutations in KCNQ1 are inherited in an autosomal dominant mode in Jervell and Lange-Nielsen syndrome, wherein severe prolongation of the QT interval is associated with increased risk of ventricular arrhythmias and congenital deafness. KCNQ1 variants are an uncommon cause of familial atrial fibrillation, characterized by uncoordinated electrical activity in the atria, as well as short QT syndrome, wherein the cardiac muscle takes less time than usual to recharge between beats. Mutations in the KCNQ1 gene have also been associated with several other conditions related to heart rhythm abnormalities, including sudden infant death syndrome (SIDS) and acquired long QT syndrome.

Clinical Sensitivity - Sequencing with CNV PGxome

Approximately 42% of all long QT syndrome cases occur due to heterozygous mutations in the KCNQ1 gene (Splawski et al. 2000).

Gross deletions and duplications in the KCNQ1 gene have been reported in patients with Long QT syndrome and Jervell and Lange-Nielsen syndrome (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the KCNQ1 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 and Jervell and Lange-Nielsen syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
KCNQ1 607542
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Cerrone M. et al. 2012. Circulation. Cardiovascular genetics. 5: 581-90. PubMed ID: 23074337
  • Human Gene Mutation Database (Bio-base).
  • Imboden M, Swan H, Denjoy I, Van Langen IM, Latinen-Forsblom PJ, Napolitano C, Fressart V, Breithardt G, Berthet M, Priori S, Hainque B, Wilde AA, Schulze-Bahr E, Feingold J, Guicheney P. 2006. Female predominance and transmission distortion in the long-QT syndrome. New England Journal of Medicine 355: 2744–2751. PubMed ID: 17192539
  • Priori et al. 2004. PubMed ID: 15367556
  • Schwartz et al. 2001. PubMed ID: 11136691
  • Splawski I. et al. 2000. Circulation. 102: 1178-85. PubMed ID: 10973849

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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