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  • Test code: 02301
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Aortopathy Comprehensive Panel

Test description

This test is a comprehensive analysis of genes associated with inherited aortopathy and related connective tissue disorders. The Invitae Aortopathy Comprehensive Panel includes genes that are associated with isolated thoracic aortic aneurysms and/or dissections (TAAD) and multi-system disorders that may have aortopathy as one feature. Given the clinical overlap between different aortopathy conditions, comprehensive testing enables a more efficient evaluation of multiple disorders based on a single indication.

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Primary panel (24 genes)

ACTA2 CBS COL3A1 COL5A1 COL5A2 EFEMP2 FBN1 FBN2 FLNA FOXE3 MED12 MYH11 MYLK NOTCH1 PLOD1 PRKG1 SKI SLC2A10 SMAD3 SMAD4 TGFB2 TGFB3 TGFBR1 TGFBR2

Add-on Preliminary-evidence Gene for Aortopathy (3 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

HCN4 MAT2A SMAD6

  • Ehlers-Danlos syndrome (EDS)
    • classic type (types I/II)
    • vascular type (type IV)
  • Loeys-Dietz syndrome (LDS)
  • Marfan syndrome and other FBN1-related conditions
  • thoracic aortic aneurysms and/or dissections (TAAD)
  • genes on this panel are also associated with other disorders

Aortopathy is a disease of the aorta. Aortopathy can be seen as an isolated feature or as part of a syndromic condition. Thoracic aortic aneurysms and dissections (TAAD) are characterized by dilatation of the ascending thoracic aorta at the level of the sinuses of Valsalva and/or ascending aorta and dissection of either the ascending or descending thoracic aorta. Aortopathy can be a presenting feature of multiple connective tissue disorders, including Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome. Additional disorders without aortopathy as a primary disease characteristic can manifest with similar or overlapping non-cardiac features associated with these connective tissue disorders.

The clinical sensitivity of this test is dependent on the underlying condition. For each condition, the chart below shows the percentage of clinical cases in which a pathogenic variant is expected to be identified in one of the genes on this panel. The clinical sensitivity is unknown for individuals with borderline or non-specific aortopathy.

Clinical sensitivity by underlying condition
TAAD Marfan syndrome Loeys-Dietz syndrome Ehlers-Danlos syndrome (vascular type)
9%-20% 70%-93% 80%-90% 90%-95%

The majority of aortopathy conditions are inherited in an autosomal dominant pattern. FLNA-related and MED12-related disorders are X-linked. Homocystinuria due to CBS deficiency, EFEMP2-related aortopathy and/or cutis laxa and SLC2A10-related arterial tortuosity syndrome are inherited in an autosomal recessive manner.

The most common causes of inherited aortopathy exhibit reduced penetrance, meaning that not everyone who inherits a predisposition to aortopathy will develop the disease. The age of onset and presenting symptoms of TAAD and related connective disorders are variable.

While aortic aneurysms are common worldwide, the exact prevalence is unknown, as they usually cause no symptoms unless they rupture. The prevalence of Marfan syndrome is 1 in 5,000 to 1 in 10,000. The prevalence of EDS, vascular type, is ~1 in 200,000.

This test may be considered for individuals with:

  • isolated TAAD
  • TAAD with clinical signs of a syndromic form of aortopathy

For links to published management guidelines for cardiology conditions, please refer to our Management guidelines page.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACTA2 NM_001613.2
CBS NM_000071.2
COL3A1 NM_000090.3
COL5A1 NM_000093.4
COL5A2 NM_000393.3
EFEMP2 NM_016938.4
FBN1 NM_000138.4
FBN2 NM_001999.3
FLNA NM_001456.3
FOXE3 NM_012186.2
HCN4 NM_005477.2
MAT2A NM_005911.5
MED12 NM_005120.2
MYH11 NM_001040113.1
MYLK NM_053025.3
NOTCH1 NM_017617.3
PLOD1 NM_000302.3
PRKG1 NM_006258.3
SKI NM_003036.3
SLC2A10 NM_030777.3
SMAD3 NM_005902.3
SMAD4 NM_005359.5
SMAD6 NM_005585.4
TGFB2 NM_003238.3
TGFB3 NM_003239.3
TGFBR1 NM_004612.2
TGFBR2 NM_003242.5; NM_001024847.2