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  • Test code: 04166
  • 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 Capillary Malformation-Arteriovenous Malformation Syndrome Test

Test description

The Invitae Capillary Malformation-Arteriovenous Malformation Test analyzes the RASA1 gene, which is associated with capillary malformation-arteriovenous malformation (CM-AVM).

Identification of a disease-causing variant would enable testing of at-risk family members, which may result in early diagnosis and treatment of arteriovenous malformations and/or arteriovenous fistulas. Early diagnosis and treatment may help avoid secondary complications and adverse outcomes.

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Primary panel (1 gene)
Add-on Hereditary Hemorrhagic Telangiectasia Genes (3 genes)

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by the presence of multiple arteriovenous malformations (AVMs). Depending on the clinical presentation of the patient, clinicians may wish to include additional genes associated with HHT for no additional charge.

ACVRL1 ENG SMAD4

  • capillary malformation-arteriovenous malformation syndrome (CM-AVM)
    • Parkes-Weber syndrome

Capillary malformation-arteriovenous malformation (CM-AVM) is a vascular disorder characterized by capillary malformations (CM) that are generally present from birth and continue to appear through childhood, into young adulthood. These CMs are generally located on the head and neck, trunk, and extremities. Approximately 35% of affected individuals are also found to have an arteriovenous malformation, an arteriovenous fistula, or Parkes-Weber syndrome.

The clinical sensitivity of pathogenic variants in RASA1 for patients with a clinical diagnosis of CM-AVM is estimated at approximately 70%.

CM-AVM is inherited in an autosomal dominant pattern. In most cases, it is inherited from an affected parent, but in 30% of cases, spontaneous de novo mutations have been reported in affected individuals with no family history of the disorder.

RASA1 pathogenic mutations show high penetrance, with a range of 90%-99%. CMs are reported in approximately 97% of individuals and AVMs in 24%-30% of individuals with RASA1 mutations. CM-AVM can have variable expressivity, even among family members.

CM-AVM is thought to occur in 1 in 100,000 individuals of northern European origin. The prevalence of this condition in other populations is unknown.

Individuals for whom this test may be appropriate include those with capillary malformations affecting the head and neck, extremities, or trunk; those with intracranial, intraspinal, extremity, or face-and-neck arteriovenous malformations or fistulas; and those with Parkes-Weber syndrome.

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
ACVRL1 NM_000020.2
ENG NM_000118.3
RASA1 NM_002890.2
SMAD4 NM_005359.5