Clinical Domain Working Groups

The Thrombosis VCEP plan to focus on curation of genes associated with Mendelian non-syndromic risk of venous thrombosis, such as protein S and C deficiencies, antithrombin deficiency (formerly antithrombin III deficiency), activated protein C resistance related to F5 and prothrombin.  The VCEP will initially focus on SERPINC1 gene, associated with antithrombin deficiency, as this gene is one of the more sequenced genes for during a thrombophilia workup.  We plan to move on to PROS1 and PROC to evaluate protein S and C deficiencies, respectively.  As more pathogenic variants have been identified in the F5 and F2 genes related to thrombophilia risk, it will also be important to evaluate these genes for pathogenic variants in addition to the well described Factor V Leiden and Prothrombin variants.

The VCEP plans to meet monthly to begin specifying the ACMG/AMP Variant Curation Guidelines for SERPINC1.  Once rule specifications are complete, we will then focus on PROS1 and PROC, which may only require minor tweaks in rule specifications due to the similar phenotype.