PROTHROMBIN G20210A

Prothrombin G20210A — affecting 2-3% of European populations, this thrombophilia variant increases DVT/PE risk 2-5 fold and guides critical decisions about anticoagulation duration, pregnancy management, and hormonal contraception.

Whole genome sequencing evaluates prothrombin G20210A alongside Factor V Leiden, protein C, protein S, antithrombin III, and all additional thrombophilia variants — providing the comprehensive coagulation genetic profile.

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About this condition

Prothrombin G20210A — Thrombophilia

Prothrombin G20210A (Factor II mutation, rs1799963) is the second most common inherited thrombophilia after Factor V Leiden, present in approximately 2-3% of European ancestry populations. The 3' UTR variant increases prothrombin mRNA stability, leading to ~30% elevated prothrombin levels and 2-5x increased risk of venous thromboembolism (DVT and PE).

Clinical impact is greatest when compounded with other thrombophilia variants. Prothrombin G20210A + Factor V Leiden heterozygosity increases VTE risk approximately 20x. Homozygous prothrombin G20210A (~1 in 10,000) confers higher risk requiring primary prophylaxis consideration. These compound genotypes change anticoagulation duration from time-limited to potentially lifelong.

Prothrombin testing has direct clinical implications for: anticoagulation duration after first VTE (extended vs. time-limited), hormonal contraception counseling (estrogen-containing contraceptives increase VTE risk further in carriers), pregnancy management (LMWH prophylaxis consideration), and surgical prophylaxis (extended anticoagulation post-operatively).

Estrogen-containing contraceptives increase VTE risk ~4x in the general population. In prothrombin G20210A carriers, this risk compounds further. Genetic testing before hormonal contraception prescribing prevents potentially fatal pulmonary embolism.

Gene locus
F2 (11p11.2)

Prothrombin G20210A testing influences anticoagulation duration, contraception counseling, pregnancy management, and surgical planning. Compound genotypes (with Factor V Leiden) require more aggressive prophylaxis.

Compound heterozygosity (prothrombin + Factor V Leiden) requires lifelong anticoagulation — WGS detects all thrombophilia variants simultaneously

A patient with isolated prothrombin G20210A and a provoked DVT may receive 3-6 months of anticoagulation. A patient with prothrombin G20210A plus Factor V Leiden heterozygosity (~20x VTE risk) requires extended or indefinite anticoagulation. Only comprehensive testing revealing all thrombophilia variants enables optimal anticoagulation duration decisions.

Pre-prescribing thrombophilia testing prevents VTE in young women starting hormonal contraception

Up to 5-8% of European women carry Factor V Leiden or prothrombin G20210A. Prescribing estrogen-containing contraceptives without genetic testing exposes carriers to preventable VTE risk. WGS-based thrombophilia screening before contraception counseling identifies women who should use progestin-only or non-hormonal alternatives.

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