Comprehensive Aortopathy Gene Panel
GTR Test Accession: Help GTR000603752.3
INHERITED DISEASEDYSMORPHOLOGYSYNDROMIC DISEASE ... View more
Last updated in GTR: 2024-05-14
Last annual review date for the lab: 2024-05-28 LinkOut
At a Glance
Diagnosis
Familial aortopathy; Acromicric dysplasia; Adams-Oliver syndrome; ...
ACTA2 (10q23.31), ADAMTS10 (19p13.2), ADAMTS17 (15q26.3), ADAMTS2 (5q35.3), AEBP1 (7p13), ...
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
Providing a genetic evaluation for patients with a personal or …
Not provided
Establish or confirm diagnosis; Predictive risk information for patient and/or family members
Ordering Information
Offered by: Help
Test short name: Help
CAORG
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Dentist
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Public Health Mandate
  • Registered Nurse
Lab contact: Help
Elyse Love, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
gcmolgen@mayo.edu
1-800-533-1710
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
https://www.mayocliniclabs.com/test-catalog/Overview/617155#Specimen
Order URL
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
Based on applicable state law
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Conditions Help
Total conditions: 54
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 48
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
Instrument
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Illumina NovaSeq 6000
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Illumina NovaSeq 6000
Clinical Information
Test purpose: Help
Diagnosis
Clinical utility: Help
Establish or confirm diagnosis
View citations (17)
  • Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. Pepin M, et al. N Engl J Med. 2000;342(10):673-80. doi:10.1056/NEJM200003093421001. PMID: 10706896.
  • Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37(3):275-81. doi:10.1038/ng1511. Epub 2005 Jan 30. PMID: 15731757.
  • Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4):452-7. doi:10.1038/ng1764. Epub 2006 Mar 19. PMID: 16550171.
  • Aneurysm syndromes caused by mutations in the TGF-beta receptor. Loeys BL, et al. N Engl J Med. 2006;355(8):788-98. doi:10.1056/NEJMoa055695. PMID: 16928994.
  • Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39(12):1488-93. doi:10.1038/ng.2007.6. Epub 2007 Nov 11. PMID: 17994018.
  • Milewicz DM, Cecchi AC. Heritable Thoracic Aortic Disease Overview. 2003 Feb 13 [updated 2023 May 04]. 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: 20301299.
  • Chen MH, Walsh CA. FLNA Deficiency. 2002 Oct 08 [updated 2021 Sep 30]. 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: 20301392.
  • Malfait F, Symoens S, Syx D. Classic Ehlers-Danlos Syndrome. 2007 May 29 [updated 2024 Feb 01]. 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: 20301422.
  • Callewaert B. Congenital Contractural Arachnodactyly. 2001 Jan 23 [updated 2022 Jul 14]. 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: 20301560.
  • Sacharow SJ, Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [updated 2017 May 18]. 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: 20301697.
  • The revised Ghent nosology for the Marfan syndrome. Loeys BL, et al. J Med Genet. 2010;47(7):476-85. doi:10.1136/jmg.2009.072785. PMID: 20591885.
  • Clinical Genome Resource: Gene-Disease Validity Classification Summary for NOTCH1-familial thoracic aortic aneurysm and aortic dissection. ClinGen; 2016. Accessed July 14, 2022. Available at https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_8269
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1120
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1213
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1244
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1386
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1524

Predictive risk information for patient and/or family members
View citations (17)
  • Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. Pepin M, et al. N Engl J Med. 2000;342(10):673-80. doi:10.1056/NEJM200003093421001. PMID: 10706896.
  • Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37(3):275-81. doi:10.1038/ng1511. Epub 2005 Jan 30. PMID: 15731757.
  • Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4):452-7. doi:10.1038/ng1764. Epub 2006 Mar 19. PMID: 16550171.
  • Aneurysm syndromes caused by mutations in the TGF-beta receptor. Loeys BL, et al. N Engl J Med. 2006;355(8):788-98. doi:10.1056/NEJMoa055695. PMID: 16928994.
  • Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39(12):1488-93. doi:10.1038/ng.2007.6. Epub 2007 Nov 11. PMID: 17994018.
  • Milewicz DM, Cecchi AC. Heritable Thoracic Aortic Disease Overview. 2003 Feb 13 [updated 2023 May 04]. 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: 20301299.
  • Chen MH, Walsh CA. FLNA Deficiency. 2002 Oct 08 [updated 2021 Sep 30]. 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: 20301392.
  • Malfait F, Symoens S, Syx D. Classic Ehlers-Danlos Syndrome. 2007 May 29 [updated 2024 Feb 01]. 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: 20301422.
  • Callewaert B. Congenital Contractural Arachnodactyly. 2001 Jan 23 [updated 2022 Jul 14]. 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: 20301560.
  • Sacharow SJ, Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [updated 2017 May 18]. 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: 20301697.
  • The revised Ghent nosology for the Marfan syndrome. Loeys BL, et al. J Med Genet. 2010;47(7):476-85. doi:10.1136/jmg.2009.072785. PMID: 20591885.
  • Clinical Genome Resource: Gene-Disease Validity Classification Summary for NOTCH1-familial thoracic aortic aneurysm and aortic dissection. ClinGen; 2016. Accessed July 14, 2022. Available at https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_8269
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1120
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1213
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1244
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1386
  • https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1524

Target population: Help
Providing a genetic evaluation for patients with a personal or family history suggestive of hereditary aortic disease. Establishing a diagnosis for a variety of hereditary conditions involving aortic disease or overlapping clinical presentations including Marfan syndrome, Loeys-Dietz syndrome, multiple forms of Ehlers-Danlos syndrome, heritable thoracic aortic disease/aortopathy, and others.
View citations (13)
  • Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. Pepin M, et al. N Engl J Med. 2000;342(10):673-80. doi:10.1056/NEJM200003093421001. PMID: 10706896.
  • Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37(3):275-81. doi:10.1038/ng1511. Epub 2005 Jan 30. PMID: 15731757.
  • Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4):452-7. doi:10.1038/ng1764. Epub 2006 Mar 19. PMID: 16550171.
  • Aneurysm syndromes caused by mutations in the TGF-beta receptor. Loeys BL, et al. N Engl J Med. 2006;355(8):788-98. doi:10.1056/NEJMoa055695. PMID: 16928994.
  • Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39(12):1488-93. doi:10.1038/ng.2007.6. Epub 2007 Nov 11. PMID: 17994018.
  • Milewicz DM, Cecchi AC. Heritable Thoracic Aortic Disease Overview. 2003 Feb 13 [updated 2023 May 04]. 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: 20301299.
  • Chen MH, Walsh CA. FLNA Deficiency. 2002 Oct 08 [updated 2021 Sep 30]. 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: 20301392.
  • Malfait F, Symoens S, Syx D. Classic Ehlers-Danlos Syndrome. 2007 May 29 [updated 2024 Feb 01]. 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: 20301422.
  • Callewaert B. Congenital Contractural Arachnodactyly. 2001 Jan 23 [updated 2022 Jul 14]. 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: 20301560.
  • Sacharow SJ, Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [updated 2017 May 18]. 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: 20301697.
  • The revised Ghent nosology for the Marfan syndrome. Loeys BL, et al. J Med Genet. 2010;47(7):476-85. doi:10.1136/jmg.2009.072785. PMID: 20591885.
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi:10.1038/gim.2015.30. Epub 2015 Mar 05. PMID: 25741868.
  • Clinical Genome Resource: Gene-Disease Validity Classification Summary for NOTCH1-familial thoracic aortic aneurysm and aortic dissection. ClinGen; 2016. Accessed July 14, 2022. Available at https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_8269
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
All detected variants are evaluated according to the most recent American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Are family members with defined clinical status recruited to assess significance of VUS without charge? Help
Contact lab for details

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Not provided. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.
Research:
Is research allowed on the sample after clinical testing is complete? Help
Research testing is only performed under IRB approved protocol with an opt-out policy in place.
Recommended fields not provided:
Technical Information
Test Procedure: Help
Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least … View more
Test Platform:
Other
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
At least 99% of the bases are covered at a read depth >30X. Sensitivity is estimated at >99% for single nucleotide variants, >94% for indels up to 39 base pairs, >95% for deletions up to 75 base pairs and insertions up to 47 base pairs.
Assay limitations: Help
Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test … View more
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Platform PT performed

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements
VUS:
Software used to interpret novel variations Help
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, SpliceAI, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations Help
All novel alterations and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
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.