Invitae Capillary Malformation-Arteriovenous Malformation Syndrome Test

Ordering
  • 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
Billing

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.

Order test

Primary panel (1 gene)

RASA1

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACVRL1 NM_000020.2
ENG NM_000118.3
RASA1 NM_002890.2
SMAD4 NM_005359.5