NM_000062.3(SERPING1):c.1420C>T (p.Gln474Ter) AND Hereditary angioedema type 1

Germline classification:: Pathogenic (1 submission)
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:: RCV000768693.1

Allele description [Variation Report for NM_000062.3(SERPING1):c.1420C>T (p.Gln474Ter)]

NM_000062.3(SERPING1):c.1420C>T (p.Gln474Ter)

Gene:

SERPING1:serpin family G member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.1

Genomic location:

Preferred name:

NM_000062.3(SERPING1):c.1420C>T (p.Gln474Ter)

HGVS:

NC_000011.10:g.57614498C>T
NG_009625.1:g.21945C>T
NM_000062.3:c.1420C>TMANE SELECT
NM_001032295.2:c.1420C>T
NP_000053.2:p.Gln474Ter
NP_000053.2:p.Gln474Ter
NP_001027466.1:p.Gln474Ter
LRG_105t1:c.1420C>T
LRG_105:g.21945C>T
LRG_105p1:p.Gln474Ter
NC_000011.9:g.57381971C>T
NM_000062.2:c.1420C>T

Protein change:

Q474*

Links:

dbSNP: rs1565174105

NCBI 1000 Genomes Browser:

rs1565174105

Molecular consequence:

NM_000062.3:c.1420C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001032295.2:c.1420C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hereditary angioedema type 1 (HAE1)
Synonyms:: Deficiency of C1 esterase inhibitor
Identifiers:: MONDO: MONDO:0015053; MedGen: C2717906; Orphanet: 100050; Orphanet: 100051; Orphanet: 91378; OMIM: 106100

Recent activity

Clear Turn Off Turn On

SRX17776895 (1)
SRA
44143556[uid] (1)
PubChem Compound

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000900063	Department of Immunology and Histocompatibility, University of Thessaly	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29753808, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000900063

Department of Immunology and Histocompatibility, University of Thessaly

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Caucasians	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency.

Loules G, Zamanakou M, Parsopoulou F, Vatsiou S, Psarros F, Csuka D, Porebski G, Obtulowicz K, Valerieva A, Staevska M, López-Lera A, López-Trascasa M, Moldovan D, Magerl M, Maurer M, Speletas M, Farkas H, Germenis AE.

Gene. 2018 Aug 15;667:76-82. doi: 10.1016/j.gene.2018.05.029. Epub 2018 May 16.

PubMed [citation]

PMID:: 29753808

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Department of Immunology and Histocompatibility, University of Thessaly, SCV000900063.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasians	4	not provided	not provided	clinical testing	PubMed (2)

Description

The c.1420C>T (p.Gln474Ter) variant has been previously reported in the literature in association with hereditary angioedema (Speletas et al., 2015; Loules et al., 2018). It is a nonsense variant that causes an interruption of the reading frame by formation of a premature stop codon in exon 8 and results in a truncated protein missing 27aa. The mutation has been detected by our laboratory in 4 patients with C1-INH HAE Type I, members of a Greek family (2 male and 2 female). It was not detected in two healthy family members that were also tested. The variant has never been detected in approximately 120000 individuals of the Exome Aggregation Consortium (ExAC) nor in 1000Genome Project, indicating that it is not a common variant. At the same location, two different variants have been previously reported in HAE database (http://hae.enzim.hu/detail.php?id=17) in association with hereditary angioedema (a) c.1420C>G (p.Gln474Glu) by Verpy et al. 1995, a missense variant that was associated with HAE when found in cis with the Leu459Arg mutation and (b) c.1420_1421insC (frameshift) by Gosswein et al. 2008, which was characterized as pathogenic for C1-INH HAE Type I. Taking all the above into account and according to ACMG Guidelines (Criteria: PVS1, PM2, PM4, PP1, PP4) the variant is considered pathogenic.

#	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		4	not provided	not provided	not provided

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine