ClinVar Miner

Submissions for variant NM_000488.4(SERPINC1):c.391C>G (p.Leu131Val)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen RCV004577659 SCV005061621 uncertain significance Hereditary antithrombin deficiency 2024-05-09 reviewed by expert panel curation The NM_000488.4:c.391C>G variant in SERPINC1 is a missense variant predicted to cause substitution of Leucine by Valine at amino acid 131 (p.Leu131Val). This variant is also known as antithrombin Southport (Legacy nomenclature: Leu99Val) in the literature. One proband from PMID: 7734360 with AT deficiency (type II-HBS) meets criteria for PP4. At least one patient with this variant displayed AT deficiency (type II- HBS) which is highly specific for SERPINC1 (PP4, PMID: 7734360). Another missense variant, c.391C>T (p.Leu131Phe), in the same codon has been classified as pathogenic for antithrombin deficiency by the ClinGen Thrombosis VCEP (PM5). The computational predictor REVEL gives a score of 0.764, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 gene function (PP3). This variant is absent from gnomAD v2.1.1-v4. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP. (Specifications version 1.0.0; date of approval: 7/17/2023)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.