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Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and Loeys-Dietz Syndrome via the TGFB3 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3983 TGFB3 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3983TGFB381479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Chun-An Chen, PhD

Clinical Features and Genetics

Clinical Features

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a disease of the heart muscle primarily affecting the right ventricle. It is characterized by myocardial atrophy, fibrofatty replacement of the ventricular myocardium and inflammatory infiltrates. 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. 1998) and affects between 1/1000 and 1/5000 people worldwide with a higher prevalence in men than women (Corrado and Thiene 2006).

Loeys-Dietz syndrome (LDS) is characterized by two major clinical features: vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus). Additional variable features include craniofacial abnormalities (ocular hypertelorism, bifid uvula/cleft palate and craniosynostosis) and cutaneous findings (translucent skin, easy bruising and dystrophic scars) (Loeys et al. 2005. PubMed ID: 15731757). Two clinical entities of LDS have been described (types 1 and 2), which represent a continuum of clinical features. Approximately 75% of patients with LDS type 1 have craniofacial manifestations, while approximately 25% of patients with LDS type 2 have cutaneous manifestations (Loeys et al. 2005. PubMed ID: 15731757; Loeys et al. 2006. PubMed ID: 16928994). LDS is usually characterized by aggressive arterial aneurysms (mean age at death is 26.1 years) and high incidence of pregnancy-related complications including death and uterine rupture (Loeys et al. 2005. PubMed ID: 15731757). Clinical features of LDS overlap with Marfan syndrome (Loeys et al. 2005. PubMed ID: 15731757; Loeys and Dietz. 2013. PubMed ID: 20301312).


ARVC/D is a heterogeneous disease that is inherited in about 50% of cases (Basso et al. 2004). Arrhythmogenic right ventricular dysplasia 1 is caused by pathogenic variants in TGFB3, and is inherited in an autosomal dominant pattern with age- and gender-dependent penetrance (Moric-Janiszewska et al. 2007). The transforming growth factor beta-3 encoded by TGFB3 is a member of the Transforming growth factor beta superfamily, which is involved in cell differentiation, embryogenesis and development. TGFB3 also plays critical roles in modulating cell adhesion and extracellular matrix formation (Kaartinen et al. 1995; Massagué et al. 2012). The TGFB3 gene contains 7 coding exons, encodes 412 amino acids and is located at 14q24.3. Most reported pathogenic variants in TGFB3 are missense or nonsense. No large deletions or duplications have been reported (Human Gene Mutation Database).

LDS is inherited in an autosomal dominant manner due to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3 (Loeys et al. 2005. PubMed ID: 15731757; Mizuguchi et al. 2004. PubMed ID: 15235604; Rienhoff et al. 2013. PubMed ID: 23824657). TGFBR1, TGFBR2, SMAD3, and TGFB2 are all involved in TGFβ signaling. TGFB2 and TGFB3 are cytokines, TGFBR1 and TGFBR2 are receptors and SMAD3 is a signal transducer and transcription factor. A combination of truncating variants (nonsense, frameshifts) and missense variants have been found in TGFB3 (Rienhoff et al. 2013. PubMed ID: 23824657; Schepers et al. 2018. PubMed ID: 29392890). Approximately 25% of LDS cases are familial and 75% of cases are de novo (Loeys and Dietz. 2013. PubMed ID: 20301312).

Clinical Sensitivity - Sequencing with CNV PG-Select

PKP2, DSP, and DSG2, account for the great majority of known genetic causes of Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (McNally et al. 2014). TGFB3 is a relatively rare cause of ARVC/D. In one ARVCD genotype-phenotype study based on an Asian population, only 1 of 53 pathogenic variants occurred in TGFB3 (Bao et al. 2013).

Approximately 95% of Loeys-Dietz cases are found to have a pathogenic variant in TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3 (Loeys and Dietz. 2013. PubMed ID: 20301312). Approximately 1-5% of cases have a pathogenic variant in TGFB2 (Loeys and Dietz. 2013. PubMed ID: 20301312).

No large deletions or duplications have been reported in TGFB3 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TGFB3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia or Loeys-Dietz syndrome and family members of patients.


Official Gene Symbol OMIM ID
TGFB3 190230
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Comprehensive Cardiac Arrhythmia Panel
Comprehensive Cardiology Panel
Familial Thoracic Aortic Aneurysm and Dissection (TAAD) Panel
Loeys-Dietz Syndrome Panel


  • Bao J. et al. 2013. Circulation. Cardiovascular Genetics. 6: 552-6. PubMed ID: 24125834
  • Basso C. et al. 2004. European Heart Journal. 25: 531-4. PubMed ID: 15039134
  • 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
  • Human Gene Mutation Database (Bio-base).
  • Kaartinen V. et al. 1995. Nature Genetics. 11: 415-21. PubMed ID: 7493022
  • Loeys B.L, Dietz H.C. 2013. Loeys-Dietz Syndrome. 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: 20301312
  • Loeys B.L. et al. 2005. Nature Genetics. 37: 275-81. PubMed ID: 15731757
  • Loeys B.L. et al. 2006. The New England Journal of Medicine. 355: 788-98. PubMed ID: 16928994
  • Massagué J. 2012. Nature Reviews. Molecular Cell Biology. 13: 616-30. PubMed ID: 22992590
  • McNally E. et al. 2014. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant. 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: 20301310
  • Mizuguchi T. et al. 2004. Nature Genetics. 36: 855-60. PubMed ID: 15235604
  • Moric-Janiszewska E., Markiewicz-Loskot G. 2007. Europace. 9: 259-66. PubMed ID: 17363426
  • Rienhoff HY et al. 2013. PubMed ID: 23824657
  • Schepers et al. 2018. PubMed ID: 29392890


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

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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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