Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen Thrombosis Variant Curation Expert Panel, |
RCV002463182 | SCV005442764 | uncertain significance | Hereditary antithrombin deficiency | 2024-12-20 | reviewed by expert panel | curation | The c.1247dup (p.Ser417LysfsTer?) variant in SERPINC1 is a frameshift variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate). This variant has been reported in at least one family meeting an antithrombin activity level of < 0.8 IU/mL and a family history of the disease with reported antithrombin levels (PS4_Supporting; PMID: 38347553). More affected individuals without the details required for scoring were reported in ClinVar (SCV002520629.1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance due to insufficient evidence for autosomal dominant hereditary antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP: PVS1_moderate, PM2_supporting, PS4_supporting. |
Laboratory for Immunogenetics and Molecular Haemostaseology, |
RCV002463182 | SCV002520629 | likely pathogenic | Hereditary antithrombin deficiency | 2022-04-14 | no assertion criteria provided | clinical testing |