The c.1273C>T variant in SERPINC1 is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 425 (p.Arg425Cys). This variant is seen with a total MAF of 0.0000006195, which meets PM2_Supporting. At least one patient with this variant displayed an antithrombin activity level of < 0.8 IU/mL on repeated independent samples, which is highly specific for hereditary antithrombin deficiency (PP4, PMID: 27098529). This variant has been reported in eight more probands with an antithrombin activity level of < 0.8 IU/mL, but not all of them had testing performed on repeated independent samples, crossed immunoelectrophoresis demonstrating an abnormal result or a family history (5.5 points awarded, PS4; PMIDs:22398878, 28300866, 23910795, 4049307, 22481271, 27098529). The variant has been reported to segregate with hereditary antithrombin deficiency in four affected family members, aside from the proband, from one family (PP1_Moderate; PMID:4049307). Another missense variant c.1274G>A (p.Arg425His) (ClinVarID:18019) in the same codon has been classified as pathogenic for hereditary antithrombin deficiency by the ClinGen Thrombosis VCEP (PM5). The computational predictor REVEL gives a score of 0.806, 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 pathogenic for autosomal dominant hereditary antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP: PS4, PP1_Moderate, PM5, PM2_Supporting, PP3, PP4.