Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000488.4(SERPINC1):c.1190C>G (p.Ser397Ter)

CA343772780

1068471 (ClinVar)

Gene: SERPINC1 (HGNC:462)

Condition: hereditary antithrombin deficiency (MONDO:0013144)

Inheritance Mode: Autosomal dominant inheritance

UUID: 6a951e51-a7df-493d-8016-6b5f271651a9

Approved on: 2025-10-21

Published on: 2026-01-22

HGVS expressions

NM_000488.4(SERPINC1):c.1190C>G (p.Ser397Ter)

NM_000488.4:c.1190C>G

NC_000001.11:g.173907478G>C

CM000663.2:g.173907478G>C

NC_000001.10:g.173876616G>C

CM000663.1:g.173876616G>C

NC_000001.9:g.172143239G>C

NG_012462.1:g.14901C>G

ENST00000367698.4:c.1190C>G

ENST00000367698.3:c.1190C>G

ENST00000617423.4:c.575C>G

NM_000488.3:c.1190C>G

NM_001365052.1:c.1046C>G

NM_001365052.2:c.1046C>G

NM_001386302.1:c.1313C>G

NM_001386303.1:c.1271C>G

NM_001386304.1:c.1169C>G

NM_001386305.1:c.1133C>G

NM_001386306.1:c.974C>G

Likely Pathogenic

PM2_Supporting PP1 PVS1_Strong PS4_Supporting

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specification: ClinGen Thrombosis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SERPINC1 Version 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.1190C>G; p.Ser397Ter variant in SERPINC1 is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong). This variant has been reported in one proband meeting an antithrombin activity level of < 0.8 IU/mL without confirmation of repeated independent samples tested, but has a family history of antithrombin activity levels of < 0.8 IU/mL (PS4_Supporting; PMID:11307839). The variant has been reported to segregate with hereditary antithrombin deficiency in two affected family members from one family (PP1; PMID:11307839). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). 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 VCEP: PVS1_Strong, PP1, PS4_Supporting, PM2_Supporting

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting)

PP1

The variant has been reported to segregate with hereditary antithrombin deficiency in two affected family members from one family (PP1; PMID:11307839).

PVS1_Strong

The c.1190C>G (p.Ser397Ter) variant in SERPINC1 is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong).

PS4_Supporting

This variant has been reported in one proband meeting an antithrombin activity level of < 0.8 IU/mL without confirmation of repeated independent samples tested, but has a family history of antithrombin activity levels of < 0.8 IU/mL (PS4_Supporting; PMID:11307839).

Curation History

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