PROS1 Cys475Tyr mutation associated with a type III protein S deficiency pattern

A 35-year-old woman presented with a deep vein thrombosis (DVT) and was diagnosed with protein S deficiency. She was treated with parenteral anticoagulation before switching to a direct oral anticoagulant. She presented to our practice 5 years later, where testing was repeated, demonstrating a type III deficiency pattern and a variant of uncertain significance in PROS1: c.1424G>A; p.Cys475Tyr. This cysteine residue participates in a disulfide bond in the sex hormone-binding globulin-like domain, which interacts with C4b-binding protein and is involved in several antithrombotic roles of protein S. This case report and the biochemical context support its pathogenicity.