Factor V Leiden (F5) R506Q Mutation

Background Information for Factor V Leiden (F5) R506Q Mutation
Characteristics: Venous thromboembolism (VTE) is a multifactorial condition caused by a combination of genetic and environmental factors. The Factor V Leiden (FVL) variant is the most common cause of inherited VTEs, accounting for over 90 percent of activated protein C (APC) resistance. Because the FVL variant eliminates the APC cleavage site, factor V is inactivated slower, thus persisting longer in blood circulation, leading to more thrombin production. Other genetic risk factors for VTE include, male sex and variants in antithrombin, protein C, protein S, or factor XIII. Non-genetic risk factors include, age, smoking, prolonged immobilization, malignant neoplasms, surgery, pregnancy, oral contraceptives, estrogen replacement therapy, tamoxifen and raloxifene therapy.
Incidence of Factor V Leiden Variant: Approximately 5 percent of Caucasians, 2 percent of Hispanics, 1 percent of African Americans and 0.5 percent of Asians are heterozygous; homozygosity occurs in 1 in 1500 Caucasians.
Inheritance: Semidominant; both heterozygotes and homozygotes are at increased risk for VTE.
Penetrance: Lifetime risk of VTE is 10 percent for heterozygotes and 80 percent for homozygotes.
Cause: The pathogenic gain of function in the F5 gene variant c.1601G>A (p.Arg534Gln). Legacy nomenclature: R506Q (1691G>A).
Clinical Sensitivity: 20-50 percent of individuals with an isolated VTE have the FVL variant.
Methodology: Polymerase chain reaction and fluorescence monitoring.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. F5 gene mutations, other than p.Arg534Gln, will not be detected.