Table 1.
Probable disease-causing variants and VUS
| Gene | Variant | No. of patients | Novel or previously-reported mutation | Probable disease-causing variant or VUS | Biologic significance |
|---|---|---|---|---|---|
| F5 (factor V) | R506Q (factor V Leiden) | 6 | Previously reported | Probable disease-causing variant | Thrombotic |
| T887S | 1 | Previously reported | VUS | Thrombotic | |
| R679Q | 1 | Novel | VUS | Disruptive to protein structure | |
| F2 (prothrombin) | G20210A (prothrombin gene mutation) | 2 | Previously reported | Probable disease-causing variant | Thrombotic |
| IVS6+5G>A | 1 | Novel | VUS | Disruptive to protein structure | |
| PROS1 (PS) | Y234C | 1 | Previously reported | Probable disease-causing variant | Thrombotic |
| P76L | 1 | Previously reported | VUS | Unlikely to be significant | |
| R233K | 1 | Previously reported | VUS | Thrombotic | |
| Homozygous S460P (Heerlen allele) | 1 | Previously reported | Probable disease-causing variant | Thrombotic | |
| R40L | 2 | Previously reported | VUS | Thrombotic | |
| PROC (PC) | R57W | 1 | Previously reported | Probable disease-causing variant | Thrombotic |
| A301S | 1 | Previously reported | Probable disease-causing variant | Thrombotic | |
| SERPINA10 (protein Z–dependent protease inhibitor) | Q384R | 1 | Previously reported | VUS | Disruptive to protein structure |
| 21_23 delCCT | 1 | Novel | VUS | Unlikely to be significant | |
| W324X | 1 | Previously reported | VUS | Disruptive to protein structure | |
| SERPINC1 (AT) | S426W | 1 | Novel | Probable disease-causing variant | Disruptive to protein structure |
| D232N | 1 | Novel | VUS | Disruptive to protein structure | |
| L131F | 1 | Previously reported | Probable disease-causing variant | Thrombotic | |
| 260 c.778_779insGAA | 1 | Novel | Probable disease-causing variant | Disruptive to protein structure | |
| c.1153+5 G>C | 1 | Novel | Probable disease-causing variant | Disruptive to protein structure | |
| SERPIND1 (heparin cofactor II) | R468C | 1 | Novel | VUS | Disruptive to protein structure |
| SERPINE2 (protease nexin-1) | M64T | 1 | Previously reported | VUS | Uncertain |
| SERPINF2 (α-2 antiplasmin) | P451S | 1 | Previously reported | VUS | Unlikely to be significant |
| HABP2 (factor VII–activating protease) | G534E (Marburg I) | 2 | Previously reported | Probable disease-causing variant | Thrombotic |
| E393Q (Marburg II) | 2 | Previously reported | VUS | Disruptive to protein structure | |
| C533F | 1 | Novel | VUS | Disruptive to protein structure | |
| S6I | 1 | Novel | VUS | Uncertain | |
| THBD (thrombomodulin) | P401L | 1 | Novel | VUS | Disruptive to protein structure |
| HRG (histidine-rich glycoprotein) | R42Q | 3 | Novel | VUS | Disruptive to protein structure |
| JAK2 (Janus kinase 2) | R1063H | 1 | Previously reported | Probable disease-causing variant | Disruptive to protein structure |
| SH2B3 (SH2B adaptor protein 3) | V402M | 1 | Previously reported | VUS | Disruptive to protein structure |
| VWF (von Willebrand factor) | P2063S | 2 | Previously reported | VUS | Unlikely to be significant |
| PLG (plasminogen) | A494V | 1 | Novel | VUS | Unlikely to be significant |
| R490Q | 1 | Novel | VUS | Unlikely to be significant | |
| TF (tissue factor) | R343W | 1 | Novel | VUS | Uncertain |
| FGA (fibrinogen α-chain) | E729Q | 1 | Previously reported | VUS | Uncertain |
| FGG (fibrinogen γ-chain) | S245F | 1 | Previously reported | VUS | Uncertain |
| CALR (calreticulin) | Y57C | 1 | Previously reported | VUS | Uncertain |
| ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif 13) | C668R | 1 | Novel | VUS | Uncertain |
| ACE (angiotensin-converting enzyme) | G354R | 1 | Novel | VUS | Uncertain |
The biologic significance of each variant was categorized as “thrombotic,” “disruptive to protein structure,” “unlikely to be significant,” or “uncertain,” based on definitions in “Methods.”