Test Catalog

Test Id : ATNGS

Antithrombin Deficiency, SERPINC1 Gene, Next-Generation Sequencing, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Ascertaining a causative alteration in SERPINC1 and the affected region of antithrombin (AT) protein in an individual clinically diagnosed with antithrombin deficiency

 

Genetic confirmation of a clinical AT deficiency diagnosis, particularly in patients with borderline low AT activity levels

 

Prognosis and risk assessment based on the genotype-phenotype correlations

 

Ascertaining alteration status of family members related to an individual with a confirmed SERPINC1 alteration 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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects pathogenic alterations in the SERPINC1 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of antithrombin (AT) deficiency based on a reduced AT activity or antigen.

 

The gene target for this test is:

Gene name (transcript): SERPINC1 (GRCh37 [hg19] NM_000488)

Chromosomal location: 1q25.1

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

The clinical workup for antithrombin deficiency begins with an antithrombin (AT) activity assay (see ATTF / Antithrombin Activity, Plasma). An abnormal result is considered less than 80% of normal activity.

 

Genetic testing for AT deficiency is indicated if:

-AT activity assay is less than 80%

-There is a clinical suspicion for hereditary deficiency of antithrombin due to family history or atypical clinical presentation

 

If AT activity results are abnormal, an antithrombin antigen assay is usually performed to determine the quantity of antithrombin present (ATTI / Antithrombin Antigen, Plasma). This is done to distinguish between type I AT deficiency (characterized by reduced AT activity and antigen) and type II AT deficiency (low activity and normal antigen).

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger sequencing when appropriate

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

SERPINC1 Gene, Full Gene NGS

Aliases
Lists additional common names for a test, as an aid in searching

Antithrombin deficiency

Antithrombin III

AT deficiency

Hereditary antithrombin deficiency

SERPINC1

Thrombophilia

Venous thromboembolism

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

The clinical workup for antithrombin deficiency begins with an antithrombin (AT) activity assay (see ATTF / Antithrombin Activity, Plasma). An abnormal result is considered less than 80% of normal activity.

 

Genetic testing for AT deficiency is indicated if:

-AT activity assay is less than 80%

-There is a clinical suspicion for hereditary deficiency of antithrombin due to family history or atypical clinical presentation

 

If AT activity results are abnormal, an antithrombin antigen assay is usually performed to determine the quantity of antithrombin present (ATTI / Antithrombin Antigen, Plasma). This is done to distinguish between type I AT deficiency (characterized by reduced AT activity and antigen) and type II AT deficiency (low activity and normal antigen).

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Genetic testing should only be considered if clinical and family history, initial coagulation screens, initial antithrombin activity and antigen tests indicate a diagnosis of antithrombin deficiency.

Shipping Instructions

1. Ambient and refrigerated specimens must arrive within 7 days, and frozen specimens must arrive within 14 days of collection.

2. Collect and package specimen as close to shipping time as possible.

Necessary Information

Rare Coagulation Disorder Patient Information is required, see Special Instructions. 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Peripheral blood

Container/Tube:

Preferred: EDTA (lavender top)

Acceptable: ACD (yellow top) or sodium citrate

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability: Ambient (preferred)/Refrigerated/Frozen

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and source of specimen.

2. Provide volume and concentration of the DNA.

Specimen Stability: Frozen (preferred)/Refrigerated/Ambient

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. Rare Coagulation Disorder Patient Information (T824) is required, see Special Instructions. Fax the completed form to 507-284-1759.

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

3. If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Extracted DNA: 100 mcL at 50 ng/mcL concentration

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred) 7 days
Frozen 14 days
Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Ascertaining a causative alteration in SERPINC1 and the affected region of antithrombin (AT) protein in an individual clinically diagnosed with antithrombin deficiency

 

Genetic confirmation of a clinical AT deficiency diagnosis, particularly in patients with borderline low AT activity levels

 

Prognosis and risk assessment based on the genotype-phenotype correlations

 

Ascertaining alteration status of family members related to an individual with a confirmed SERPINC1 alteration 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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects pathogenic alterations in the SERPINC1 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of antithrombin (AT) deficiency based on a reduced AT activity or antigen.

 

The gene target for this test is:

Gene name (transcript): SERPINC1 (GRCh37 [hg19] NM_000488)

Chromosomal location: 1q25.1

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

The clinical workup for antithrombin deficiency begins with an antithrombin (AT) activity assay (see ATTF / Antithrombin Activity, Plasma). An abnormal result is considered less than 80% of normal activity.

 

Genetic testing for AT deficiency is indicated if:

-AT activity assay is less than 80%

-There is a clinical suspicion for hereditary deficiency of antithrombin due to family history or atypical clinical presentation

 

If AT activity results are abnormal, an antithrombin antigen assay is usually performed to determine the quantity of antithrombin present (ATTI / Antithrombin Antigen, Plasma). This is done to distinguish between type I AT deficiency (characterized by reduced AT activity and antigen) and type II AT deficiency (low activity and normal antigen).

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Antithrombin (AT) deficiency is a rare hereditary thrombophilia that puts patients at a significantly increased risk of venous thromboembolism. In selected cases, patients manifest heparin resistance. Individuals with AT deficiency are at increased risk for venous thromboembolism (VTE) and late (2nd or 3rd trimester) pregnancy loss.(1,2) It has been estimated that individuals with inherited AT deficiency have a 16-fold increase in risk of VTE compared to individuals without AT deficiency.(4) Women with AT deficiency are at particularly high risk for developing clots during pregnancy and after delivery.(5)

 

Hereditary AT deficiency is uncommon, with prevalence in the general population of 1 in 2000 to 5000.(1, 2) Hereditary AT deficiency is inherited in an autosomal dominant manner with variable penetrance. Both men and women may be affected.

 

AT deficiency is a result of defects in the concentration or function of AT, a natural anticoagulant in blood plasma. AT is the major inhibitor of blood coagulation by inactivating thrombin and factor Xa. The SERPINC1 gene encodes for antithrombin. Genetic testing of SERPINC1 is indicated if plasma AT activity assay is abnormally low (ie, typically less than 80% of normal or lower than the reference range established in the local laboratory). AT activity testing should not be performed during acute thrombosis or illness as these could cause a temporary reduction in AT levels. Likewise, it should not be performed while the patient is taking an anticoagulant such as heparin (which may falsely lower levels) or an oral direct factor Xa inhibitor (eg, rivaroxaban, apixaban or edoxaban), which may falsely elevate AT levels.

 

Additionally, causes of acquired (non-genetic) AT deficiency are much more common than inherited AT deficiency and should be excluded prior to genetic testing. These causes of acquired AT deficiency include liver disease, acute thrombosis, heparin therapy, nephrotic syndrome, disseminated intravascular coagulation, and effects of chemotherapeutic agents such an L-asparaginase. These and other acquired causes of AT deficiency should be excluded prior to genetic testing.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Consultations with the Mayo Clinic Special Coagulation Clinic, Molecular Hematopathology Laboratory, and Thrombophilia Center are available for DNA diagnosis cases. This may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical:

Some individuals may have a mutation that is not identified by the methods performed. The absence of a mutation, therefore, does not eliminate the possibility of antithrombin (AT) deficiency. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies (VAF) significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Technical Limitations:

Next-generation sequencing (NGS) may not detect all types of genetic variants. Additionally, rare polymorphisms may be present that could lead to false negative or positive results. Therefore test results should be interpreted in the context of antithrombin activity and antigen measurements, clinical findings, family history, and other laboratory data. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If multiple alterations are identified, NGS is not able to distinguish between alterations that are found in the same allele ("in cis") and alterations found on different alleles ("in trans"). This limitation may complicate diagnosis or classification and has implications for inheritance and genetic counseling. To resolve these cases, molecular results must be correlated with clinical history, activity and antigen measurements, and family studies.

 

Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Patnaik MM, Moll S: Inherited Antithrombin deficiency: a review. Haemophilia 2008;14(6):1229-1239

2. Blajchamn MA, Austin RC, Fernandez-Rachubinski F, et al: Blood 1992;80(9):2159-2171

3. Patnaik MM, Guenther J, Pruthi RK, et al: The Potential Role of Molecular Analysis in Hereditary Antithrombin (AT) Deficiency Diagnosis and Management. Blood 2009;114:2976 (Abstract)

4. Di Minno MN, Ambrosino P, Ageno W, et al: Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies. Thromb Haemost 2015;135(5):923-932

5. Rogenhofer N, Bohlmann MK, Beuter-Winkler P, et al: Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency. Ann Hematol 2014;93(3):385-392

6. Luxembourg B, Delev D, Geisen C, et al: Molecular basis of antithrombin deficiency. Thromb Haemost 2011;105(4):635-646

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing and/or Sanger sequencing are performed.

 

Regions of homology, high guanine-cytosine (GC)-rich content, and repetitive sequences may not provide accurate sequence. Therefore, all reported alterations detected by next-generation sequencing in these regions are confirmed by an independent reference method. However, this does not rule out the possibility of a false-negative result in these regions.

 

Sanger sequencing is used to confirm alterations detected by next-generation sequencing when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

21 to 28 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks; DNA: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81479

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ATNGS SERPINC1 Gene, Full Gene NGS 93814-2
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
606391 ATNGS Result 50397-9
606392 Alterations Detected 82939-0
606393 Interpretation 69047-9
606394 Additional Information 48767-8
606395 Method 85069-3
606396 Disclaimer 62364-5
606397 Panel Gene List 48018-6
606398 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports