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.
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 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:
Recommendations on when to test an individual for thrombophilias including antithrombin III have been suggested:
For management guidelines, please refer to:
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|