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]

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Variant: NM_001386306.1:c.391C>G

CA343777244

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bf29d89c-2a5c-456b-ac84-147ac3439b9b

Approved on: 2024-05-09

Published on: 2024-05-09

HGVS expressions

NM_001386306.1:c.391C>G

NC_000001.11:g.173914570G>C

CM000663.2:g.173914570G>C

NC_000001.10:g.173883708G>C

CM000663.1:g.173883708G>C

NC_000001.9:g.172150331G>C

NG_012462.1:g.7809C>G

ENST00000367698.4:c.391C>G

ENST00000367698.3:c.391C>G

ENST00000487183.1:n.96C>G

ENST00000494024.1:n.617C>G

ENST00000617423.4:c.391C>G

NM_000488.3:c.391C>G

NM_001365052.1:c.247C>G

NM_000488.4:c.391C>G

NM_001365052.2:c.247C>G

NM_001386302.1:c.391C>G

NM_001386303.1:c.472C>G

NM_001386304.1:c.391C>G

NM_001386305.1:c.391C>G

Uncertain Significance

PP3 PP4 PM5 PM2_Supporting

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

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)

PP3

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.

PP4

At least one patient with this variant displayed AT deficiency (type II- HBS) which is highly specific for SERPINC1 (PP4, PMID: 7734360)

PM5

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 and meets criteria for PM5.

PM2_Supporting

This variant is absent from gnomAD v2.1.1-v4

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