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HelpTest Code GNANT Antithrombin Deficiency, SERPINC1 Gene, Next-Generation Sequencing, Varies
Ordering Guidance
This test should only be considered if clinical and family history, initial coagulation screens, and/or initial antithrombin (AT) activity and antigen testing results suggest a diagnosis of antithrombin deficiency (see Testing Algorithm).
This test does not measure AT activity levels. For assessment of AT activity, order ATTF / Antithrombin Activity, Plasma.
If genetic testing for hereditary blood clotting disorders using a larger panel is desired, a 16-gene comprehensive thrombosis panel is available; order GNTHR / Thrombosis Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies.
Testing for the SERPINC1 gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known variants testing) is available for the SERPINC1 gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
Rare Coagulation Disorder Patient Information is required. Testing may proceed without the patient information; however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.
Specimen Required
Specimen Type: Whole blood
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Forms
1. Rare Coagulation Disorder Patient Information (T824) is required.
2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
3. If not ordering electronically, complete, print, and send an Coagulation Test Request (T753) with the specimen.
Useful For
Evaluating antithrombin AT deficiency in patients with a personal or family history suggestive of this hereditary thrombophilia
Confirming an AT deficiency diagnosis with the identification of a known or suspected disease-causing alteration in the SERPINC1 gene, particularly in patients with borderline low AT activity levels
Determining the disease-causing alteration within the SERPINC1 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of AT deficiency
Prognosis and risk assessment based on the genotype-phenotype correlations
Ascertaining the variant status of family members related to an individual with a confirmed SERPINC1 variant for the purposes of informing clinical management and genetic counseling
Evaluating individuals with apparent heparin resistance
This test is not intended for prenatal diagnosis.
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the SERPINC1 gene associated with antithrombin (AT) deficiency, a rare hereditary blood clotting disorder. See Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for AT deficiency.
Testing Algorithm
The clinical workup for antithrombin (AT) deficiency should begin with an AT activity assay.
Genetic testing for AT deficiency is indicated if:
-AT activity assay is less than 80% of normal (Note: reference range may vary depending on the locally established reference range)
-There is a clinical suspicion of hereditary thrombophilia and possible AT deficiency due to family history or atypical clinical presentation
-Acquired (nongenetic) causes of AT deficiency have been excluded (eg, liver disease, acute thrombosis, heparin therapy, nephrotic syndrome, disseminated intravascular coagulation, and chemotherapeutic agents such an L-asparaginase)
Note: Low AT levels may be temporarily associated with other conditions such severe trauma, severe burns, or the presence of acute blood clots.
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
SERPINC1 Gene, Full Gene NGSSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Antithrombin (AT) deficiency is a rare hereditary blood clotting disorder (thrombophilia) associated with germline variants in the SERPINC1 gene. It is inherited in an autosomal dominant manner with variable penetrance; both men and women may be affected. The prevalence varies widely, with estimates between 1 in 500 to 1 in 5000 individuals.(1-3)
AT deficiency is characterized by defects in the concentration or function of AT, a natural anticoagulant in blood plasma. It leads to the highest risk of venous thromboembolism among the known inherited thrombophilias. In some cases, patients have resistance to heparin therapy. Affected women have a particularly elevated risk for pregnancy-related complications, including thromboembolic events during pregnancy and after delivery, as well as fetal loss.(4-7)
Acquired (nongenetic) AT deficiency is more common than inherited AT deficiency and should be excluded prior to genetic testing. Causes of acquired AT deficiency include liver disease, acute thrombosis, heparin therapy, nephrotic syndrome, disseminated intravascular coagulation, and chemotherapeutic agents, such an L-asparaginase.(4,8)
The British Society for Haematology provides guidelines regarding diagnosis, management, and laboratory testing for individuals with hereditary thrombophilias including AT deficiency.(9)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(10) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Day(s) Performed
Varies
Report Available
28 to 42 daysSpecimen Retention Time
Whole blood: 2 weeks (if available); Extracted DNA: 3 monthsPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| GNANT | SERPINC1 Gene, Full Gene NGS | 93814-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 619006 | Test Description | 62364-5 |
| 619007 | Specimen | 31208-2 |
| 619008 | Source | 31208-2 |
| 619009 | Result Summary | 50397-9 |
| 619010 | Result | 82939-0 |
| 619011 | Interpretation | 59465-5 |
| 619012 | Additional Results | 82939-0 |
| 619013 | Resources | 99622-3 |
| 619014 | Additional Information | 48767-8 |
| 619015 | Method | 85069-3 |
| 619016 | Genes Analyzed | 82939-0 |
| 619017 | Disclaimer | 62364-5 |
| 619018 | Released By | 18771-6 |