Submissions for variant NM_000488.4(SERPINC1):c.953C>T (p.Pro318Leu)

dbSNP: rs1460568494

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen	RCV000851915	SCV004037390	pathogenic	Hereditary antithrombin deficiency	2023-09-21	reviewed by expert panel	curation	The NM_000488.4(SERPINC1):c.953C>T variant predicts a Pro318Leu missense change. It is absent from gnomAD v2.1.1 and v3.1.2, meeting criteria for PM2_Supporting. It has a REVEL score of 0.956 and meets PP3 (threshold >0.6). At least 2 probands with AT deficiency (and repeat sampling) are reported in the literature (PP4) and 8 probands with AT deficiency and a positive family history are noted from internal VCEP data, meeting criteria for PS4_Very Strong. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PS4_Very Strong, PP3, PP4, PM2_Supporting.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851915	SCV000899996	likely pathogenic	Hereditary antithrombin deficiency	2019-02-01	criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV000851915	SCV002499586	likely pathogenic	Hereditary antithrombin deficiency		criteria provided, single submitter	clinical testing