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Progressive Familial Heart Block via the TRPM4 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
11773 TRPM4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11773TRPM481479 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.

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

Progressive familial heart block is a genetic condition that alters the normal beating of the heart. It can be divided into type IA, type IB and type II, based on the location of heart signaling interruption and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node (Fernandez et al. 2004; Lee et al. 2011).

Progressive familial heart block type I (PFHBI) is an autosomal dominant cardiac bundle branch disease that may progress to complete heart block. In electrocardiograph, PFHBI could be indicated by right bundle branch block, left anterior or posterior hemiblock, or complete heart block, with broad QRS complexes (Daumy et al. 2016). Affected people may have shortness of breath, dizziness, fainting, heart failure, or sudden death. The implantation of a pacemaker or electrocardiographic follow-up are treatment options. Progressive familial heart block type IB (PFHB1B) is caused by heterozygous pathogenic variants in the TRPM4 gene (Liu et al. 2010).

Genetics

Pathogenic variants in TRPM4 lead to Progressive Familial Heart Block type 1B (PFHB1B), which is inherited in an autosomal dominant pattern. TRPM4 encodes the Ca2+-activated nonselective cation channel of the transient receptor potential melastatin ion channel family and contains 25 exons, encodes 1214 amino acids and spans over 54 kb in Chromosome 19q13.33. TRPM4 transcripts can be detected ubiquitously in the human heart and, in particular, within the Purkinje fibers, a key structure for cardiac conduction. Pathogenic variants increase current density due to an elevated TRPM4 channel density at the cell surface secondary to impaired endocytosis and deregulation of SUMOylation (Kruse et al. 2009; Liu et al. 2010). So far, all reported pathogenic variants in TRPM4 are single nucleotide substitutions (missense or nonsense) (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in TRPM4 were identified in ~5% of unrelated heritable arrhythmia probands with various ECG phenotypes (Stallmeyer et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the TRPM4 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 cardiac conduction defect are candidates for this test.

Gene

Official Gene Symbol OMIM ID
TRPM4 606936
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Progressive Familial Heart Block Type 1B AD 604559

Citations

  • Daumy X. et al. 2016. International Journal of Cardiology. 207: 349-58. PubMed ID: 26820365
  • Fernandez P. et al. 2004. Cardiovascular Journal of South Africa. 15: 129-32. PubMed ID: 15258623
  • Human Gene Mutation Database (Bio-base).
  • Kruse M. et al. 2009. The Journal of Clinical Investigation. 119: 2737-44. PubMed ID: 19726882
  • Lee C.K. et al. 2011. Korean Circulation Journal. 41: 276-9. PubMed ID: 21731570
  • Liu H. et al. 2010. Circulation. Cardiovascular Genetics. 3: 374-85. PubMed ID: 20562447
  • Stallmeyer B. et al. 2012. Human Mutation. 33: 109-17. PubMed ID: 21887725

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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