Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen Thrombosis Variant Curation Expert Panel, |
RCV000019631 | SCV005061624 | likely pathogenic | Hereditary antithrombin deficiency | 2024-05-09 | reviewed by expert panel | curation | The c.235C>A variant in SEPRINC1 is a missense variant predicted to cause substitution of arginine by serine at amino acid 79 (p.Arg79Ser). This variant has been reported in one family with an abnormal crossed immunoelectrophoresis assay demonstrating decreased antithrombin function. (PS4_Supporting; PMID:3350974). This variant is absent from gnomAD v[2.1.1] (PM2_Supporting). This variant resides within a region, Arg79, of SERPINC1 that is defined as a critical functional domain that would impact heparin binding site residues by the ClinGen Thrombosis Variant Curation Expert Panel (PM1). Another missense variant c.236G>A (p.Arg79His) (ClinVarID:18014) in the same codon has been classified as pathogenic for hereditary antithrombin deficiency by the ClinGen Thrombosis Variant Curation Expert Panel (PM5). The computational predictor REVEL gives a score of 0.718, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal dominant hereditary antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis Variant Curation Expert Panel: PM1, PM5, PP3, PM2_Supporting, PS4_Supporting. (Required: ClinGen Thrombosis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SERPINC1 Version 1.0.0; date of approval) |
OMIM | RCV000019631 | SCV000039929 | pathogenic | Hereditary antithrombin deficiency | 1990-06-18 | no assertion criteria provided | literature only |