NM_000488.3(SERPINC1):c.500A>C (p.Asn167Thr) AND Antithrombin III deficiency

Clinical significance:Pathogenic (Last evaluated: Nov 29, 2012)

Review status:(1/4)1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000019657.26

Allele description [Variation Report for NM_000488.3(SERPINC1):c.500A>C (p.Asn167Thr)]

Gene:
SERPINC1:serpin peptidase inhibitor, clade C (antithrombin), member 1 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
1q25.1
Genomic location:
Preferred name:
NM_000488.3(SERPINC1):c.500A>C (p.Asn167Thr)
HGVS:
  • NC_000001.11:g.173911923T>G
  • NG_012462.1:g.10456A>C
  • NM_000488.3:c.500A>C
  • NP_000479.1:p.Asn167Thr
  • NC_000001.10:g.173881061T>G
Protein change:
N135T; ASN135THR
Links:
OMIM: 107300.0045; dbSNP: 121909570
NCBI 1000 Genomes Browser:
rs121909570
Molecular consequence:
  • NM_000488.3:c.500A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Antithrombin III deficiency (AT3D)
Synonyms:
Thrombophilia due to antithrombin III deficiency; Thrombophilia due to antithrombin deficiency; ATD: Antithrombin deficiency
Identifiers:
MedGen: C0272375; OMIM: 613118

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000039955OMIMPathogenic
(Nov 29, 2012)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Familial overexpression of beta antithrombin caused by an Asn135Thr substitution.

Bayston TA, Tripodi A, Mannucci PM, Thompson E, Ireland H, Fitches AC, Hananeia L, Olds RJ, Lane DA.

Blood. 1999 Jun 15;93(12):4242-7.

PubMed [citation]
PMID:
10361121

Details of each submission

From OMIM, SCV000039955.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 25-year-old Italian woman who had experienced no thrombosis and had no family history of venous thrombosis, Bayston et al. (1999) found antithrombin deficiency (613118) with borderline levels (approximately 70% antigen and activity) of antithrombin. Direct sequencing of amplified DNA showed a mutation in codon 135, AAC to ACC, predicting a heterozygous asn135-to-thr substitution. This substitution altered the predicted consensus sequence for glycosylation, asn-X-ser, adjacent to the heparin interaction site of antithrombin. Antithrombin isolated from plasma of the patient by heparin-Sepharose chromatography contained amounts of beta-antithrombin (the very high affinity fraction) greatly increased (approximately 20 to 30% of total) above the trace levels found in normals. Expression of the residue 135 variant in both a cell-free system and COS-7 cells confirmed altered glycosylation arising as a consequence of the mutation. Wildtype and variant protein were translated and then exported from COS-7 cells with apparently equal efficiency, in contrast to the reduced level of variant observed in plasma of the affected individual. This case represented a novel cause of antithrombin deficiency, removal of glycosylation consensus sequence, and highlighted the potentially important role of beta-antithrombin in regulating coagulation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2014

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