Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the DSG2 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
11265 DSG2 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11265DSG281406 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

Clinical Features and Genetics

Clinical Features

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart disease primarily affecting the right ventricle. It is characterized by myocardial atrophy, fibrofatty replacement of the ventricular myocardium and inflammatory infiltrates (McNally et al. GeneReviews, 2009). With disease progression and occasional left ventricle involvement, heart failure may result. The most common symptoms include ventricular arrhythmias, recurrent syncope, seizures and sudden death after physical or emotional stress. ARVC/D is present in ~20% of young sudden cardiac death victims (Corrado et al. N Engl J Med 339:364-369, 1998). ARVC/D affects between 1/1000 and 1/5000 people worldwide with a higher prevalence in men compared to women (Corrado and Thiene Circulation 113:1634-1637, 2006).

Genetics

ARVC/D is a heterogeneous disease that is inherited in about 50% of the cases (Basso et al. Eur Heart J 25:531-534, 2004). The mode of inheritance is most often autosomal dominant with age- and gender-dependent penetrance. Autosomal recessive variants of ARVC/D with hair and skin abnormalities have also been described (Protonotarios et al. Br Heart J 56:321-326, 1986). To date, eight genes, including DSG2, have been implicated in autosomal dominant ARVC/D (Pilichou et al. Circulation 113:1171-9, 2006). Mutations in four genes encoding desmosomal proteins, PKP2, DSP, DSG2 and DSC2 account for the majority of known genetic causes of ARVC/D (Bhuiyan et al. Circ Cardiovasc Genet 2:418-427, 2009; den Haan et al. Circ Cardiovasc Genet 2:428-435, 2009). Over 60 heterozygous DSG2 causative mutations, distributed throughout the entire coding region, have been reported. The majority of causative variants are missense mutations, however, nonsense, small insertions or deletions, and splicing mutations have also been reported. ARVC/D patients with compound heterozygous mutations in the DSG2 gene or digenic mutations in the DSG2 and DSC2 genes have been reported (Awad et al. Am J Hum Genet 79:136-142, 2006). In addition to ARVC/D, a heterozygous deletion in DSG2 has also been found in a patient with dilated cardiomyopathy (Garcia-Pavia et al. Heart 97:1744-52, 2011).

The DSG2 gene encodes the desmoglein-2 protein, an important component of the cardiac desmosome that is expressed only in the myocardium.

Clinical Sensitivity - Sequencing with CNV PGxome

This test will detect causative mutations in ~10% of patients with clinical diagnosis of ARVC/D (Pilichou et al. Circulation 113:1171-1179, 2006; Syrris et al. Eur Heart J 28:581-588, 2007).

Testing Strategy

This test provides full coverage of all coding exons of the DSG2 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

Patients with autosomal dominant ARVC/D.

Gene

Official Gene Symbol OMIM ID
DSG2 125671
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Awad, M. M., et.al. (2006). "DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy." Am J Hum Genet 79(1): 136-42. PubMed ID: 16773573
  • Basso C. et al. 2004. European Heart Journal. 25: 531-4. PubMed ID: 15039134
  • Bhuiyan ZA et al. 2009. Circulation. Cardiovascular Genetics. 2: 418-27. PubMed ID: 20031616
  • Corrado D. et al. 1998. The New England Journal of Medicine. 339: 364-9. PubMed ID: 9691102
  • Corrado D., Thiene G. 2006. Circulation. 113: 1634-7. PubMed ID: 16585401
  • den Haan, AD., et al. (2009) "Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy." Circ Cardiovasc Genet 2(5):428-35 PubMed ID: 20031617
  • Elizabeth McNally (2009). "Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant." PubMed ID: 20301310
  • Garcia-Pavia et al. (2011) Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study. Heart 97(21):1744-52 PubMed ID: 21859740
  • Pilichou, K., et.al. (2006). "Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy." Circulation 113(9): 1171-9. PubMed ID: 16505173
  • Protonotarios, N., et.al. (1986). "Cardiac abnormalities in familial palmoplantar keratosis." Br Heart J 56(4): 321-6. PubMed ID: 2945574
  • Syrris, P., et.al. (2007). "Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease." Eur Heart J 28(5): 581-8. PubMed ID: 17105751

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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