NM_000488.4(SERPINC1):c.1121A>G (p.Asp374Gly) AND Hereditary antithrombin deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003447783.1

Allele description [Variation Report for NM_000488.4(SERPINC1):c.1121A>G (p.Asp374Gly)]

NM_000488.4(SERPINC1):c.1121A>G (p.Asp374Gly)

Gene:

SERPINC1:serpin family C member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.1

Genomic location:

Preferred name:

NM_000488.4(SERPINC1):c.1121A>G (p.Asp374Gly)

HGVS:

NC_000001.11:g.173909584T>C
NG_012462.1:g.12795A>G
NM_000488.4:c.1121A>GMANE SELECT
NM_001365052.2:c.977A>G
NM_001386302.1:c.1244A>G
NM_001386303.1:c.1202A>G
NM_001386304.1:c.1100A>G
NM_001386305.1:c.1064A>G
NM_001386306.1:c.905A>G
NP_000479.1:p.Asp374Gly
NP_000479.1:p.Asp374Gly
NP_001351981.1:p.Asp326Gly
NP_001373231.1:p.Asp415Gly
NP_001373232.1:p.Asp401Gly
NP_001373233.1:p.Asp367Gly
NP_001373234.1:p.Asp355Gly
NP_001373235.1:p.Asp302Gly
LRG_577t1:c.1121A>G
LRG_577:g.12795A>G
LRG_577p1:p.Asp374Gly
NC_000001.10:g.173878722T>C
NM_000488.3:c.1121A>G

Protein change:

D302G

Molecular consequence:

NM_000488.4:c.1121A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001365052.2:c.977A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386302.1:c.1244A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386303.1:c.1202A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386304.1:c.1100A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386305.1:c.1064A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386306.1:c.905A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary antithrombin deficiency (AT3D)
Synonyms:: Antithrombin III deficiency; Thrombophilia due to antithrombin III deficiency; Reduced antithrombin III activity; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013144; MedGen: C0272375; OMIM: 613118; Human Phenotype Ontology: HP:0001976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004175529	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22398878, 33401890, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004175529

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 19, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis and genotype-phenotype correlation in patients with antithrombin deficiency from Southern Italy.

Castaldo G, Cerbone AM, Guida A, Tandurella I, Ingino R, Tufano A, Ceglia C, Di Minno MN, Ruocco AL, Di Minno G.

Thromb Haemost. 2012 Apr;107(4):673-80. doi: 10.1160/TH11-09-0671. Epub 2012 Mar 8.

PubMed [citation]

PMID:: 22398878

Novel Mutation p.Asp374Val of SERPINC1 in a Turkish Family with Inherited Antithrombin Deficiency

Aslan D.

Turk J Haematol. 2021 Jun 1;38(2):161-163. doi: 10.4274/tjh.galenos.2021.2020.0702. Epub 2021 Jan 6. No abstract available.

PubMed [citation]

PMID:: 33401890
PMCID:: PMC8171213

See all PubMed Citations (3)

Details of each submission

From Genetics and Molecular Pathology, SA Pathology, SCV004175529.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The SERPINC1 c.1121A>G variant is classified as a VUS (PS4_Supporting, PM2, PP3) The SERPINC1 c.1121A>G variant is a single nucleotide change in exon 5/7 of the SERPINC1 gene, which is predicted to change the amino acid aspartic acid at position 374 in the protein to glycine. The variant has been reported in a patient with Antithrombin deficiency (PMID:22398878) (PS4_Supporting). This variant is absent from population databases (PM2). An additional patient with antithrombin deficiency has also been reported at this residue (p.Asp374Val)(Aslan et al 2021, PMID: 33401890). Computational predictions support a deleterious effect on the gene or gene product (PP3). The variant has been reported in the HGMD database: CM125929. It has not been reported in dbSNP or ClinVar.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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