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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7261 F2 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7261F281479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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