Invitae Antithrombin III Deficiency Test


Test description

Antithrombin III deficiency is an adult-onset hereditary condition that is a result of pathogenic variants in the SERPINC1 gene. This disorder causes an increased risk of deep venous thrombosis and pulmonary embolism.

Genetic testing of the SERPINC1 gene may establish or confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also enable testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)


Alternative tests to consider

Testing for antithrombin III deficiency is also included in the broader Invitae Hereditary Thrombophilia Panel. Depending on the individual’s clinical and family history, this broader panel may be appropriate and can be ordered at no additional charge.

Antithrombin III deficiency

Antithrombin III deficiency is an adult-onset inherited condition that predisposes an individual to blood-clot formation. This condition is associated with an increased risk of blood clots in deep veins, especially in the legs (deep vein thrombosis). These clots can break off and block blood flow through blood vessels in other parts of the body like the lungs (where it would cause a pulmonary embolism). Women with antithrombin III deficiency also have an increased risk of miscarriage and other pregnancy complications.

Pathogenic variants in the SERPINC1 gene are identified in approximately 83% of affected individuals.

Antithrombin III deficiency is inherited in an autosomal dominant pattern.

While most people with antithrombin III deficiency never develop abnormal blood clots, certain factors can increase the risk, including advanced age, trauma, immobilization, and pregnancy. Having another inherited blood-clotting disorder in addition to antithrombin III deficiency can also influence the risk of abnormal blood clotting.

The lifetime risk of individuals with antithrombin III deficiency developing thrombosis is 28 times greater than that of the general population.

The prevalence of antithrombin III deficiency is approximately 7-20 per 10,000 individuals in the general population. Antithrombin III deficiency is present in 0.5%-3% of individuals presenting with venous thromboembolism.

Analysis of the SERPINC1 gene may be considered in individuals with the following:

  • venous thromboembolism (VTE) at an unusual site (e.g., cerebral mesenteric, portal, hepatic)
  • recurrent VTE
  • idiopathic VTE (unrelated to surgery/trauma)
  • VTE under the age of 50
  • VTE during pregnancy or in the postpartum period
  • recurrent fetal loss, especially in the second or third trimesters
  • VTE while on oral contraceptives, hormone replacement, or methotrexate
  • life-threatening venous thrombosis (e.g., pulmonary embolism, cerebral vein thrombosis)
  • a family history of VTE in first-degree relatives
  • a family history of antithrombin III deficiency

Recommendations on when to test an individual for thrombophilias including antithrombin III have been suggested:

  1. Baglin, T, et al. Clinical guidelines for testing for heritable thrombophilia. Br. J. Haematol. 2010; 149(2):209-20. doi: 10.1111/j.1365-2141.2009.08022.x. PMID: 20128794
  2. Caspers, M, et al. Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort. Thromb. Haemost. 2012; 108(2):247-57. doi: 10.1160/TH11-12-0875. PMID: 22627591
  3. Crowther, MA, Kelton, JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann. Intern. Med. 2003; 138(2):128-34. doi: 10.7326/0003-4819-138-2-200301210-00014. PMID: 12529095
  4. Lijfering, WM, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood. 2009; 113(21):5314-22. doi: 10.1182/blood-2008-10-184879. PMID: 19139080
  5. Martinelli, I, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood. 1998; 92(7):2353-8. PMID: 9746774
  6. Reich, LM, et al. Role of the geneticist in testing and counseling for inherited thrombophilia. Genet. Med. 2003; 5(3):133-43. doi: 10.1097/01.GIM.0000067987.77803.D0. PMID: 12792420
  7. Varga, EA, Kujovich, JL. Management of inherited thrombophilia: guide for genetics professionals. Clin. Genet. 2012; 81(1):7-17. doi: 10.1111/j.1399-0004.2011.01746.x. PMID: 21707594

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
SERPINC1 NM_000488.3