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_000488.3(SERPINC1):c.914C>A (p.Pro305His)

CA1251311

597303 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cbdbee38-f5df-4dea-a641-e7961a17dd29

HGVS expressions

NM_000488.3:c.914C>A

NM_000488.3(SERPINC1):c.914C>A (p.Pro305His)

NC_000001.11:g.173909791G>T

CM000663.2:g.173909791G>T

NC_000001.10:g.173878929G>T

CM000663.1:g.173878929G>T

NC_000001.9:g.172145552G>T

NG_012462.1:g.12588C>A

ENST00000367698.4:c.914C>A

ENST00000367698.3:c.914C>A

ENST00000487183.1:n.565C>A

ENST00000617423.4:c.559+2073C>A

NM_001365052.1:c.770C>A

NM_000488.4:c.914C>A

NM_001365052.2:c.770C>A

NM_001386302.1:c.1037C>A

NM_001386303.1:c.995C>A

NM_001386304.1:c.893C>A

NM_001386305.1:c.857C>A

NM_001386306.1:c.698C>A

NM_000488.4(SERPINC1):c.914C>A (p.Pro305His)

Benign

BA1 BS2

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 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.914C>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of proline by histidine at amino acid 305 (p.Pro305His). The highest population minor allele frequency in gnomAD v2.1.1 is 0.008133 (249/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.002]) for BA1, and therefore meets this criterion (BA1). This variant has been observed in nine individuals, of Indian heritage, with normal normal antithrombin levels, five of which showed normal levels with repeat testing (BS2; PMID: 27161325). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BA1, BS2.

BA1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.008133 (249/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.002]) for BA1, and therefore meets this criterion (BA1).

BS2

This variant has been observed in nine individuals, of Indian heritage, with normal normal antithrombin levels, five of which showed normal levels with repeat testing (BS2; PMID: 27161325).

Approved on: 2023-07-25

Published on: 2023-09-29

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