Factor 5 Leiden (F5) R506Q Mutation

BACKGROUND INFORMATION: Prothrombin Factor II mutation increases prothrombin levels and is associated with an increased risk of thrombosis, with heterozygotes having a 2-4 fold increase in risk of thrombosis. The expression of Factor II Prothrombin thrombophilia is impacted by coexisting genetic thrombophilic disorders (malignancy, factor V Leiden, antithrombin II deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, high factor VIII levels), and circumstances including: pregnancy, oral contraceptive use, hormone replacement therapy, selective estrogen receptor modulators, travel, central venous catheters, surgery, transplantation and advanced age.

INCIDENCE: Approximately 2-5 percent of Caucasians, 0.3 percent of African Americans, and is uncommon in other ethnic or racial groups; polymorphism is present in 5-18% of patients with spontaneous thromboembolism. Homozygosity occurs in approximately 1 in 10,000 individuals.

  • INHERITANCE: Incomplete penetrance autosomal dominant
  • PENETRANCE: Lifetime Risk of thrombosis is 2-4 fold for heterozygotes. Homozygosity increases the levels of risk above that seen in heterozygotes.
  • CAUSE: A single base pair substitution Factor II 20210G>A.
  • NOTE: Standardized nomenclature for the Factor II mutation is F2 c.20210G>A.
  • CLINICAL SENSITIVITY AND SPECIFICITY: 10 and 91 percent, respectively.
  • METHODOLOGY: Multiplex PCR using eSensor technology (IVD).
  • ANALYTICAL SENSITIVITY AND SPECIFICITY: 99 percent.
  • LIMITATIONS:  Rare diagnostic errors can occur due to primer site mutations. F2 gene mutations, other than G20210A, will not be detected.
  • The performance characteristics of this test were verified by Delta Pathology MDx.  The U.S. Food and Drug Administration (FDA) has approved this test for clinical use.
  • Counseling and informed consent are recommended for genetic testing.