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Hereditary Hemorrhagic Telangiectasia
Clinical Genetic Test
Help
offered by
Impact Genetics
View lab's test page
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GTR Test Accession: Help GTR000500010.17
NYS CLEP
INHERITED DISEASECARDIOVASCULARDYSMORPHOLOGY ... View more
Last updated in GTR: 2022-11-08
View version history
Last annual review date for the lab: 2023-10-11 LinkOut
At a Glance
Test purpose: Help
Diagnosis; Monitoring; Mutation Confirmation; ...
Conditions (5): Help
Hereditary hemorrhagic telangiectasia; Hereditary hemorrhagic telangiectasia type 3; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; ...
Genes (3): Help
ACVRL1 (12q13.13), ENG (9q34.11), SMAD4 (18q21.2)
Methods (3): Help
Molecular Genetics - Deletion/duplication analysis: Multiplex Ligation-dependent Probe Amplification (MLPA); ...
Target population: Help
The HHT diagnosis is classified as definite if three criteria …
Clinical validity: Help
The test detects a mutation in over 91% of patients …
Clinical utility: Help
Avoidance of invasive testing; Establish or confirm diagnosis; Lifestyle planning; ...
Ordering Information
Offered by: Help
Impact Genetics
View lab's website
View lab's test page
Test short name: Help
HHT
Specimen Source: Help
  • Amniocytes
  • Amniotic fluid
  • Buccal swab
  • Cell culture
  • Chorionic villi
  • Cord blood
  • Fetal blood
  • Fibroblasts
  • Isolated DNA
  • Peripheral (whole) blood
  • Product of conception (POC)
  • Saliva
  • Skin
  • Urine
  • White blood cell prep
  • View specimen requirements
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Registered Nurse
Test Order Code: Help
Available via LabCorp for U.S. Customers: HHT Proband = 480074
View other test codes
LOINC codes: Help
**LOINC codes notice
CPT codes: Help
**AMA CPT codes notice

Copyright: 2023 American Medical Association. All rights reserved.

Lab contact: Help
Jaime Jessen, MSc, CGC, Certified Genetic counselor, CGC, Genetic Counselor
jessenj@dynacare.ca
647-631-3266
Contact Policy: Help
Post-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
Pre-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
How to Order: Help
Canada: E-mail info@impactgenetics.com that a sample is being sent. Download, fill in, and include HHT required forms (available at www.impactgenetics.com). Prepare the HHT Sample as per the guidelines provided. Ship the HHT Sample to us for testing.

U.S.A.: Download, fill in and include HHT required forms (available at www.impactgenetics.com) …
View more
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Data Storage and Backup
Maternal cell contamination study (MCC)
Result interpretation
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
    Comment: We offer high sensitivity analysis suitable for finding low-level mosaic mutatons
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
Yes
Test strategy: Help
We use MLPA for exon copy number analysis, and sequence analysis of all exons and nearby flanking intronic regions, for the ACVRL1 and ENG genes until a causative mutation is found. The 5' UTR region of ENG is included in sequencing analysis. If no mutation is found we also sequence … View more
View citations (2)
  • Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8. doi:10.1136/jmg.2006.042606. Epub 2006 May 11. PMID: 16690726.
  • Lee NP, Matevski D, Dumitru D, Piovesan B, Rushlow D, Gallie BL. Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48(5):353-7. doi:10.1136/jmg.2010.088112. Epub 2011 Mar 17. PMID: 21415079.
Pre-test genetic counseling required: Help
No
Post-test genetic counseling required: Help
No
Conditions Help
Total conditions: 5
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 3
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 3
Method Category Help
Test method Help
Instrument
Deletion/duplication analysis
Multiplex Ligation-dependent Probe Amplification (MLPA)
Applied Biosystems 3730 capillary sequencing instrument
RNA analysis
RT-PCR and cDNA sequencing
Sequence analysis of the entire coding region
Bi-directional Sanger Sequence Analysis
Applied Biosystems 3730 capillary sequencing instrument
Clinical Information
Test purpose: Help
Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Predictive; Prognostic; Risk Assessment; Screening; Therapeutic management
Clinical validity: Help
The test detects a mutation in over 91% of patients meeting at least three Curaçao criteria. At least two other chromosomal regions are expected to be involved in HHT. When a test is developed for these regions we will re-test all samples with no mutation found and re-issue reports with … View more
View citations (1)
  • Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8. doi:10.1136/jmg.2006.042606. Epub 2006 May 11. PMID: 16690726.
Clinical utility: Help
Avoidance of invasive testing
View citations (2)
  • McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301525.
  • https://www.ncbi.nlm.nih.gov/books/NBK1351

Establish or confirm diagnosis
View citations (2)
  • McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301525.
  • https://www.ncbi.nlm.nih.gov/books/NBK1351

Lifestyle planning
View citations (2)
  • McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301525.
  • https://www.ncbi.nlm.nih.gov/books/NBK1351

Predictive risk information for patient and/or family members
View citations (2)
  • McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301525.
  • https://www.ncbi.nlm.nih.gov/books/NBK1351

Reproductive decision-making
View citations (2)
  • McDonald J, Stevenson DA. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301525.
  • https://www.ncbi.nlm.nih.gov/books/NBK1351

Target population: Help
The HHT diagnosis is classified as definite if three criteria are present, Possible or Suspected if two criteria are present, and Unlikely if fewer than two criteria are present. The Curaçao criteria include the following: Epistaxis – Spontaneous, recurrent nosebleeds Telangiectases – Multiple at characteristic sites (lips, oral cavity, fingers, … View more
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
If a VUS is found we first continue to analyze all exons of the genes tested. If no other mutation is found to be disease causing, we analyze the VUS. A literature and database review is performed for every VUS. Where appropriate splice site analysis and missense variant analysis algorithms … View more

Are family members with defined clinical status recruited to assess significance of VUS without charge? Help
Yes. Our lab will indicate which family members will be useful for our analysis. Samples requested by our lab will not be subject to charge.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes. Once the recruited family members are tested, we will issue a new report to the ordering physician detailing resultant assessment of the novel variation.
Research:
Is research allowed on the sample after clinical testing is complete? Help
If consent is given by the patient for the use of their sample, de-identified samples may be used in research.
Recommended fields not provided:
Sample negative report, Sample positive report
Technical Information
Test Procedure: Help
Copy number analysis by MLPA, and sequence analysis of exons. Reverse-transcriptase PCR RNA analysis where indicated
View citations (1)
  • Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8. doi:10.1136/jmg.2006.042606. Epub 2006 May 11. PMID: 16690726.
Test Platform:
None/not applicable
Test Confirmation: Help
A new dilution of the stock patient DNA is tested using the same or different method
Test Comments: Help
Our current test sensitivity for patients with confirmed HHT (Curaçao criteria) is 91%. We are also able to detect mosaic mutations at a level of 20%.
Availability: Help
Tests performed
Entire test performed in-house

Test performance comments
The entire test is performed in our CAP & CLIA certified laboratory. State Licence: Maryland Pennsylvania State Licence pending: Florida California NY (pending)
Analytical Validity: Help
Sensitivity to detect ENG, ACVRL1 or SMAD4 mutation in patients with clinically confirmed HHT: 91%. This test is validated to detect over 99% of described mutations.
View citations (1)
  • Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8. doi:10.1136/jmg.2006.042606. Epub 2006 May 11. PMID: 16690726.
Assay limitations: Help
Cannot detect large deletions or duplications at mosaic levels below 25%. The likelihood of the involvement of additional genes means that until these genes are identified we will not achieve 100% sensitivity.
View citations (2)
  • Prigoda NL, Savas S, Abdalla SA, Piovesan B, Rushlow D, Vandezande K, Zhang E, Ozcelik H, Gallie BL, Letarte M. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8. doi:10.1136/jmg.2006.042606. Epub 2006 May 11. PMID: 16690726.
  • Lee NP, Matevski D, Dumitru D, Piovesan B, Rushlow D, Gallie BL. Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48(5):353-7. doi:10.1136/jmg.2010.088112. Epub 2011 Mar 17. PMID: 21415079.
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Intra-Laboratory

PT Provider: Help
Internal blinded samples

Description of PT method: Help
Our proficiency testing program specifically for HHT includes: testing samples previously or concurrently tested at another laboratory, sending samples tested at our lab to another lab with known qualifications and comparable methods, and testing blinded samples previously tested in our lab. Participation in a formal PT program, (EMQN) for RB, … View more
VUS:
Software used to interpret novel variations Help
SIFT, Polyphen-2, AlignGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, Human Splicing Finde

Laboratory's policy on reporting novel variations Help
A report is sent which indicates the level of uncertainty and asks for samples from parents, or other relatives as appropriate.
Recommended fields not provided:
Description of internal test validation method, Major CAP category, CAP category, CAP test list
Regulatory Approval
FDA Review: Help
Category: Not Applicable
NYS CLEP Approval: Help
Number: 7175554
Status: Approved
Additional Information

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.