Test 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.
Secondary ID
619005Useful 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.
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
Specimen 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.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.
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the SERPINC1 gene, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the SERPINC1 gene.
There may be regions of the SERPINC1 gene that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)
The reference transcript for the SERPINC1 gene is NM_000488.3. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
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 RochesterCPT 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 |