Prothrombin/Factor II Deficiency via the F2 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7261 | F2 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Congenital prothrombin/Factor II deficiency is an inherited bleeding disorder. Phenotypically there are two presentations of the disease. Type I deficiency/hypoprothrombinemia individuals display reduced Factor II levels whereas type II deficiency/dysprothrombinemia individuals have normal levels but impaired Factor II activity (Lancellotti et al. 2013; Peyvandi et al. 2012). Complete deficiency of prothrombin is incompatible with life (Sun et al. 1998). Onset age is variable with disease severity correlating to Factor II activity levels. Common symptoms include mucocutaneous bleeding, epistaxis, menorrhagia, easy bruising, hemarthroses, and soft tissue bleeding. In severe forms of prothrombin deficiency, intracranial hemorrhage or umbilical bleeding may present and be life threatening. Mild forms of the disorder are typically asymptomatic with disease becoming apparent after patients incur trauma or surgical procedures. Deficiency in factor II may also be acquired through vitamin K deficiency, autoimmune disease, or loss of anticoagulant factors protein C and S (Vivaldi et al. 1997; Napolitano et al. 2010). Symptoms also mirror several other factor deficiency disorders. Genetic testing may aid in differential diagnosis of the various coagulation factor deficiencies and between congenital and acquired forms of Factor II deficiency. Several therapies may be employed to curtain symptoms including Factor II protein concentrates and immunosuppressive drugs (Lechler 1999).
Genetics
Prothrombin deficiency is inherited in an autosomal recessive manner through mutations in the F2 gene. Missense mutations are causative for prothrombin deficiency in ~80% of cases and primarily disrupt the catalytic serine protease domain (Akavan et al. 2000; Lancellotti et al. 2013). Small insertions, deletions, splice site, and nonsense mutations account for the remaining causative mutations with gross deletions being documented in a sole case of the disease (Wong et al. 2006). Prothrombin is activated by factor X and V to form active thrombin. Thrombin can both promote and inhibit clot formation. Active thrombin facilitates clotting through promotion of fibrin clot formation and also activates protein C, an inhibitor of the coagulation cascade. Single variant testing for Prothrombin G20210A, a founder mutation causing increased coagulability and risk for thrombosis, is also available (Kujovich 1993).
Clinical Sensitivity - Sequencing with CNV PG-Select
Sequencing is capable of detecting >95% of causative mutations within the F2 gene (Lancellotti et al. 2013). Clinical Sensitivity is problematic to predict as only a small number of patients have been documented with prothrombin deficiency and because several acquired disorders also may present with low prothrombin plasma levels.
Testing Strategy
This test provides full coverage of all coding exons of the F2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Patients with Factor II deficiency typically have prolonged partial thromboplastin time (PTT) and prothrombin time (PT). However, depending on the extent of Factor II deficiency these results may appear normal (Lancellotti et al. 2013). The best candidates have decreased Factor II levels or activity, or have a positive family history for the disorder. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in F2.
Patients with Factor II deficiency typically have prolonged partial thromboplastin time (PTT) and prothrombin time (PT). However, depending on the extent of Factor II deficiency these results may appear normal (Lancellotti et al. 2013). The best candidates have decreased Factor II levels or activity, or have a positive family history for the disorder. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in F2.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| F2 | 176930 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Prothrombin Deficiency, Congenital | AR | 613679 |
Related Tests
| Name |
|---|
| Bleeding Disorders Panel |
| Coagulation Factor Deficiency Panel |
Citations
- Akhavan S, Mannucci PM, Lak M, Mancuso G, Mazzucconi MG, Rocino A, Jenkins PV, Perkins SJ. 2000. Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency. Thromb. Haemost. 84: 989–997. PubMed ID: 11154146
- Kujovich JL. 2014. Prothrombin-Related Thrombophilia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301327
- Lancellotti S, Basso M, Cristofaro R De. 2013. Congenital prothrombin deficiency: an update. Semin. Thromb. Hemost. 39: 596-606. PubMed ID: 23852823
- Lechler E. 1999. Use of prothrombin complex concentrates for prophylaxis and treatment of bleeding episodes in patients with hereditary deficiency of prothrombin, factor VII, factor X, protein C protein S, or protein Z. Thromb. Res. 95: S39–50. PubMed ID: 10499908
- Napolitano M, Mariani G, Lapecorella M. 2010. Hereditary combined deficiency of the vitamin K-dependent clotting factors. Orphanet J Rare Dis 5: 21. PubMed ID: 20630065
- Peyvandi F, Bolton-Maggs PHB, Batorova A, Moerloose P De. 2012. Rare bleeding disorders. Haemophilia 18 Suppl 4:148-153. PubMed ID: 22726099
- Sun WY, Witte DP, Degen JL, Colbert MC, Burkart MC, Holmbäck K, Xiao Q, Bugge TH, Degen SJ. 1998. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc. Natl. Acad. Sci. U.S.A. 95: 7597–7602. PubMed ID: 9636195
- Vivaldi P, Rossetti G, Galli M, Finazzi G. 1997. Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome. Case report and review of literature. Haematologica 82: 345–347. PubMed ID: 9234588
- Wong AYK, Hewitt J, Clarke BJ, Hudson DM, Krisinger MJ, Dower NA, MacGillivray RTA. 2006. Severe prothrombin deficiency caused by prothrombin-Edmonton (R-4Q) combined with a previously undetected deletion. J. Thromb. Haemost. 4: 2623–2628. PubMed ID: 17002658
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.