Thrombophilia (factor V Leiden, prothrombin)

rs6025 · rs1799963

Factor V Leiden (F5) and the prothrombin G20210A variant (F2) are associated with increased risk of venous thrombosis. Their individual relevance depends in part on genotype, family history and other clinical factors. A result from a genomic file is not enough to diagnose a condition or decide on medication or prevention.

Key points

Factor V Leiden (rs6025 A allele) makes factor V resistant to breakdown by activated protein C.
The prothrombin variant (rs1799963 A allele) raises the prothrombin level and thus the tendency to clot.
The degree of risk depends on genotype and other individual factors.

#Two mechanisms

Factor V Leiden changes the site where activated protein C normally slows clotting factor V; the braking mechanism works less well, clotting runs longer. The prothrombin variant G20210A lies in the non-coding region and leads to more prothrombin in blood. Both shift the balance toward clot formation.

#What it means

Genotype, age, prior thrombosis, family history, other health conditions and additional circumstances can change the assessment. Homozygosity or carrying both variants may be interpreted differently from a single heterozygous variant. Questions about hormone therapy, pregnancy, surgery or travel should be discussed with a clinician.

#Context

Genotyping from sequencing data can have technical limitations and is not automatically a clinical thrombophilia test. Genome displays assessed variants as technical evidence; diagnosis and any implications require medical assessment.

What Genome measures. The genotypes at rs6025 (factor V Leiden) and rs1799963 (prothrombin G20210A), where they can be assessed in the data.

Sources

1Bertina et al., 1994 Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64-67. doi.org/10.1038/369064a0
2Poort et al., 1996 A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698-3703. doi.org/10.1182/blood.V88.10.3698.bloodjournal88103698