| Entity/subtype | Molecular defect | Inheritance/acquired status | Typical phenotype/risk | Recommended laboratory confirmation | Ontology/gene identifiers |
|---|---|---|---|---|---|
| Factor V Leiden thrombophilia | **F5** c.1601G>A, p.Arg534Gln (legacy R506Q; historically 1691G>A); causes activated protein C resistance | Autosomal dominant thrombophilia susceptibility; incomplete penetrance | Common inherited thrombophilia; increased risk of first and recurrent venous thromboembolism, especially with estrogen exposure, pregnancy, surgery, or immobility (pqac-00000007, pqac-00000009) | APC resistance assay as screen, followed by targeted **F5** genotyping (pqac-00000007) | **F5**; thrombophilia **MONDO:0002305**; inherited thrombophilia **MONDO:0100240** (pqac-00000000) |
| Prothrombin thrombophilia | **F2** c.*97G>A (legacy G20210A) in 3' UTR; associated with higher prothrombin levels | Autosomal dominant thrombophilia susceptibility; incomplete penetrance | Increased venous thromboembolism risk; risk may be amplified by coexisting provoking factors or additional thrombophilia variants (pqac-00000007, pqac-00000009) | Targeted **F2** genotyping for c.*97G>A | **F2**; thrombophilia **MONDO:0002305**; inherited thrombophilia **MONDO:0100240** (pqac-00000000) |
| Antithrombin deficiency | Loss-of-function or reduced-activity variants in **SERPINC1** causing quantitative or qualitative antithrombin deficiency | Usually autosomal dominant inherited thrombophilia | High-risk hereditary thrombophilia with strong VTE predisposition; events often occur at younger age and may recur (pqac-00000003, pqac-00000010) | Initial antithrombin **activity** assay; if low, antigen assay and activity:antigen interpretation; consider molecular testing; test outside anticoagulant interference/acquired deficiency states (pqac-00000009) | **SERPINC1**; thrombophilia **MONDO:0002305**; inherited thrombophilia **MONDO:0100240** (pqac-00000000) |
| Protein C deficiency | Pathogenic variants in **PROC** with reduced protein C anticoagulant activity | Usually autosomal dominant inherited thrombophilia; severe biallelic disease can present neonatally | Increased VTE risk; severe deficiency may cause neonatal purpura fulminans (human and model evidence) (pqac-00000000) | Protein C activity with confirmatory antigen/genetic testing as appropriate; avoid testing during acute thrombosis or anticoagulant interference when possible (pqac-00000009) | **PROC**; thrombophilia **MONDO:0002305**; inherited thrombophilia **MONDO:0100240** (pqac-00000000) |
| Protein S deficiency | Pathogenic variants in **PROS1** causing reduced free/functional protein S | Usually autosomal dominant inherited thrombophilia | Increased VTE risk; severe deficiency can contribute to purpura fulminans; platelet and plasma protein S both modulate venous thrombosis biology (pqac-00000000) | Free protein S antigen and/or functional assay with careful interpretation; confirm genetically when indicated; avoid confounding by pregnancy, estrogen use, and anticoagulants (pqac-00000009) | **PROS1**; thrombophilia due to protein S deficiency **MONDO:0012868**; inherited thrombophilia **MONDO:0100240** (pqac-00000000) |
| Antiphospholipid syndrome (APS) | Autoantibody-mediated thrombophilia: lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies | Acquired | Venous and arterial thrombosis and pregnancy morbidity; triple-positive profile confers higher recurrence risk and often changes anticoagulant choice (pqac-00000008, pqac-00000010) | Persistent antiphospholipid antibody positivity on repeat testing per APS criteria; include lupus anticoagulant, anticardiolipin, anti-β2GPI; interpret carefully with anticoagulants present (pqac-00000008, pqac-00000009) | APS is an acquired thrombophilia; broader thrombophilia **MONDO:0002305** |
| Not recommended marker set | Common **MTHFR** polymorphisms (e.g., C677T, A1298C) | Genetic variants of low/uncertain thrombosis relevance | **Not recommended** as routine thrombophilia markers because evidence does not support meaningful VTE risk stratification in most settings (pqac-00000009) | Do **not** include in standard thrombophilia panels unless a separate indication exists (pqac-00000009) | **MTHFR**; not a core recommended thrombophilia marker (pqac-00000009) |


*Table: Compact reference table of the principal inherited and acquired thrombophilia entities, their molecular basis, clinical significance, and laboratory confirmation. It is useful for report standardization and for distinguishing core markers from tests such as MTHFR polymorphisms that are not routinely recommended.*