ClinVar Miner

Submissions for variant NM_000488.4(SERPINC1):c.448dup (p.Gln150fs)

dbSNP: rs1572090305
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen RCV000819059 SCV005367709 pathogenic Hereditary antithrombin deficiency 2024-07-03 reviewed by expert panel curation The c.448dup (p.Gln150ProfsTer27) variant in SERPINC1 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 3/7 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in one probands meeting an antithrombin activity level of < 0.8 without confirmation of repeated independent samples tested but with a family history of antithrombin activity levels of < 0.8 IU/mL (PS4_Supporting; PMID:28300866). The variant has been reported to segregate with hereditary antithrombin deficiency in two additional affected family members from one family (PP1; PMID:28300866). This variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting). 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: PVS1, PM2_Supporting, PS4_Supporting, PP1.
Labcorp Genetics (formerly Invitae), Labcorp RCV000819059 SCV000959701 pathogenic Hereditary antithrombin deficiency 2018-07-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln150Profs*39) in the SERPINC1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SERPINC1-related disease. Loss-of-function variants in SERPINC1 are known to be pathogenic (PMID: 21264449). For these reasons, this variant has been classified as Pathogenic.

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