Order Code GNTHR Thrombosis Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies

Ordering Guidance

Special coagulation testing for evaluating patients with thrombosis or hypercoagulability states should be performed prior to genetic testing. For more information see AATHR / Thrombophilia Profile, Plasma and Whole Blood.

This test is designed to evaluate a variety of thrombophilia.

This test is not designed to evaluate for a single common hereditary thrombosis disorder, such as when an individual has a known family history of antithrombin deficiency, protein C deficiency, or protein S deficiency, specifically. If testing for a particular common hereditary thrombosis disorder is desired, single gene tests are available for the SERPINC1, PROC, and PROS1 genes. See GNANT / Antithrombin Deficiency, SERPINC1 Gene, Next-Generation Sequencing, Varies; GNPRC / Protein C Deficiency, PROC Gene, Next-Generation Sequencing, Varies; or GNPRS / Protein S Deficiency, PROS1 Gene, Next-Generation Sequencing, Varies.

This test is not designed to evaluate for hereditary bleeding disorders. If bleeding is the indication for testing and testing for hereditary bleeding disorders is desired, bleeding panels are available. See GNBLF / Bleeding Disorders, Focused Gene Panel, Next-Generation Sequencing, Varies or GNBLC / Bleeding Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies

Customization of this panel and single gene analysis for any gene present on this panel are 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 mutations testing) is available for the genes on this panel. 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 hereditary thrombosis in patients with a personal or family history suggestive of a hereditary thrombosis disorder

Confirming a hereditary thrombosis disorder diagnosis with the identification of a known or suspected pathogenic alteration in one or more of 16 genes associated with a variety of hereditary thrombosis disorders

Determining the disease-causing alterations within one or more of these 16 genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of a thrombosis disorder

Identifying the causative alteration for genetic counseling purposes

Prognosis and risk assessment based on the genotype-phenotype correlations

Carrier testing for close family members of an individual with a hereditary thrombosis disorder diagnosis

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 16 genes associated with a variety of hereditary thrombosis disorders: ADAMTS13, F2, F5, FGA, FGB, FGG, HRG, PIGA, PLAT, PLG, PROC, PROCR, PROS1, SERPINC1, SERPIND1, and THBD. See Targeted Genes and Methodology Details for Thrombosis Disorders, Comprehensive Gene Panel and 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 a variety of hereditary thrombosis disorders.

Testing Algorithm

A systematic diagnosis through conventional coagulation testing is recommended prior to considering genetic testing for any suspected thrombosis disorder.

Genetic testing for a hereditary thrombosis disorder is indicated if:

-Coagulation tests indicate a deficiency or functional abnormality (note these tests are best performed in medically stable patients who are not receiving particular anticoagulants)

-There is a clinical suspicion for a hereditary thrombosis disorder due to family history or atypical clinical presentation

-Acquired causes of deficiencies associated with thrombosis have been excluded (eg, vitamin K deficiency, oral anticoagulation with coumarin compounds, liver disease, intravascular coagulation and fibrinolysis/disseminated intravascular coagulation)

However, no screening test exists for detecting defects in a subset of genes on this panel, such as PROCR and THBD. If the thrombotic tendency is a concern, a set of clinical guidelines from the British Society for Haematology on testing for heritable thrombophilia is freely available.(1)

Special Instructions

Method Name

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

Reporting Name

Thrombosis Comprehensive Panel, NGS

Specimen Type

Varies

Specimen 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.

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 genes analyzed, 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 genes analyzed.

There may be regions of genes 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. See Targeted Genes and Methodology Details for Thrombosis Disorders, Comprehensive Gene Panel and Methodology Details for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

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.

Genes analyzed: ADAMTS13, F2, F5, FGA, FGB, FGG, HRG, PIGA, PLAT, PLG, PROC, PROCR, PROS1, SERPINC1, SERPIND1, and THBD

Day(s) Performed