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Hereditary Hemorrhagic Telangiectasia Type 2 (HHT2) via the ACVRL1/ALK1 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
11065 ACVRL1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11065ACVRL181479 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. 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

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Hereditary hemorrhagic telangiectasia (HHT, OMIM 187300) is a disease of vascular dysplasia. HHT is characterized by the presence of arteriovenous malformations (AVMs) that involve direct connections between arteries and veins with no intervening capillary bed. AVMs can be located throughout the body and have a greater tendency towards rupture than normal blood vessels; this is often visible as telangiectases (small red or purple spots) on the lips, hands, or face of HHT patients. Recurrent nosebleeds are the most common symptom of HHT. About 20-25% of patients develop GI bleeding later in life that may lead to severe anemia (Abdalla et al. J Med Genet 40:494-502, 2003). Hepatic AVMs are found in up to 32% of patients and are often asymptomatic but can cause cirrhosis and affect cardiac output (Plauchu et al. Am J Med Genet 32:291-297, 1989; Garcia-Tsao et al. New Eng J Med 343:931-936, 2000). Cerebral AVMs (5-20% of patients) and pulmonary AVMs (30-50% of patients) are usually present at birth and may cause headaches, seizures, ischemia, hypoxemia, and hemothorax (see Shovlin and Letarte Thorax 54:714-729, 1999). The penetrance of HHT varies depending upon type (see below), and symptoms usually present by age 16 (Porteous et al. J Med Genet 29:527-530, 1992). The severity of HHT can vary widely even within families and can go unnoticed in affected individuals.

Genetics

HHT is an autosomal dominant disorder caused by variants in genes encoding proteins that modulate the normally inhibitory transforming growth factor (TGF)-ß signaling pathway during cell proliferation and differentiation. The incidence of HHT is 1 in about 5,000 to 8,000 individuals and affects men, women, and all ethnic groups (Govani and Shovlin Eur J Hum Genet 17:860-871, 2009). Variants in the ACVRL1/ALK1 gene (OMIM 601284) account for ~ 40% of cases (HHT2; OMIM 600376). ACVRL1/ALK1 encodes activin receptor like kinase 1 (ALK1), which is a type I receptor in endothelial cells that binds (TGF)-ß when coexpressed with a type II receptor (Johnson et al. Nat Genet 13:189, 1996). HHT2 generally has a lower penetrance, milder phenotype, later onset of disease, and a higher occurrence of hepatic AVMs but lower occurrence of pulmonary or cerebral AVMs than HHT1 (Letteboer et al. J Med Genet 43:371-377, 2006). Over 300 causative variants have been identified throughout the ACVRL1 gene and include primarily missense/nonsense variants. Large whole or multi-exon deletions and splicing variants are rare (Prigoda et al. J Med Genet 43:722-728, 2006). No predominant variant has been identified.

Clinical Sensitivity - Sequencing with CNV PGxome

Variants in the ACVRL1 gene are found in ~ 40% of HHT patients.

Testing Strategy

This test provides full coverage of all coding exons of the ACVRL1 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

Individuals with frequent nosebleeds, telangiectases, or any degree of GI, pulmonary, or cerebral bleeding.

Gene

Official Gene Symbol OMIM ID
ACVRL1 601284
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hereditary Hemorrhagic Telangiectasia Type 2 AD 600376

Citations

  • Abdalla, S. A., et.al. (2003). "Visceral manifestations in hereditary haemorrhagic telangiectasia type 2." J Med Genet 40(7): 494-502. PubMed ID: 12843319
  • Garcia-Tsao, G., et.al. (2000). "Liver disease in patients with hereditary hemorrhagic telangiectasia." N Engl J Med 343(13): 931-6. PubMed ID: 11006369
  • Govani, F. S., Shovlin, C. L. (2009). "Hereditary haemorrhagic telangiectasia: a clinical and scientific review." Eur J Hum Genet 17(7): 860-71. PubMed ID: 19337313
  • Johnson et al. Nat Genet 13:189, 1996 PubMed ID: 8640225
  • Letteboer, T. G., et.al. (2006). "Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia." J Med Genet 43(4): 371-7. PubMed ID: 16155196
  • Plauchu, H., et.al. (1989). "Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population." Am J Med Genet 32(3): 291-7. PubMed ID: 2729347
  • Porteous, M. E., et.al. (1992). "Hereditary haemorrhagic telangiectasia: a clinical analysis." J Med Genet 29(8): 527-30. PubMed ID: 1518020
  • Prigoda, N. L., et.al. (2006). "Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations." J Med Genet 43(9): 722-8. PubMed ID: 16690726
  • Shovlin, C. L., Letarte, M. (1999). "Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms." Thorax 54(8): 714-29. PubMed ID: 10413726

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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