NM_000505.4(F12):c.983C>A (p.Thr328Lys) AND Hereditary angioneurotic edema

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 17, 2015
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:: RCV000222890.4

Allele description

NM_000505.4(F12):c.983C>A (p.Thr328Lys)

Genes:

F12:coagulation factor XII [Gene - OMIM - HGNC]
SLC34A1:solute carrier family 34 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_000505.4(F12):c.983C>A (p.Thr328Lys)

Other names:

F12, THR309LYS; Thr328Lys

HGVS:

NC_000005.10:g.177404231G>T
NG_007568.1:g.10346C>A
NM_000505.4:c.983C>AMANE SELECT
NP_000496.2:p.Thr328Lys
NP_000496.2:p.Thr328Lys
LRG_145t1:c.983C>A
LRG_145:g.10346C>A
LRG_145p1:p.Thr328Lys
NC_000005.9:g.176831232G>T
NM_000505.3:c.983C>A
P00748:p.Thr328Lys

Note:

NCBI staff reviewed the sequence information reported in PubMed 16638441 to determine the location of this allele on current reference sequence (T328K).

Protein change:

T328K

Links:

UniProtKB: P00748#VAR_031501; OMIM: 610619.0006; dbSNP: rs118204456

NCBI 1000 Genomes Browser:

rs118204456

Molecular consequence:

NM_000505.4:c.983C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary angioneurotic edema (HAE)
Synonyms:: Angioedemas, Hereditary; ANGIOEDEMA, HEREDITARY, TYPE I; C1 esterase inhibitor deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019623; MedGen: C0019243; Orphanet: 91378; OMIM: PS106100

Recent activity

Clear Turn Off Turn On

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
SCV000271369	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Sep 17, 2015)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 19178938, 17825897, 20490261, 19474702, 25790805, 25744496, 16638441, 17186468, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271369

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Sep 17, 2015)

germline

clinical testing

PubMed (9)
[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	not provided	2	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic analysis of Factor XII and bradykinin catabolic enzymes in a family with estrogen-dependent inherited angioedema.

Duan QL, Binkley K, Rouleau GA.

J Allergy Clin Immunol. 2009 Apr;123(4):906-10. doi: 10.1016/j.jaci.2008.12.010.

PubMed [citation]

PMID:: 19178938

Hereditary angioedema with normal C1 inhibitor gene in a family with affected women and men is associated with the p.Thr328Lys mutation in the F12 gene.

Martin L, Raison-Peyron N, Nöthen MM, Cichon S, Drouet C.

J Allergy Clin Immunol. 2007 Oct;120(4):975-7. Epub 2007 Sep 7. No abstract available.

PubMed [citation]

PMID:: 17825897

See all PubMed Citations (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271369.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Thr328Lys variant in F12 has been reported in at least 18 individuals with hereditary angioedema type 3 (HAE 3), and segregated with disease in >35 affect ed relatives (Dewald 2006, Cichon 2006, Martin 2007, Duan 2009, Picone 2010, Mor eno 2015, Firinu 2015). However, many apparently unaffected family members were also found to carry this variant, which has been partially attributed to both ag e- and sex-dependent penetrance (Dewald 2006, Martin 2007). Of note, the HAE 3 p henotype appears to be estrogen-dependent and males who carry this variant were rarely affected (Dewald 2006, Martin 2007). The p.Thr328Lys variant was also ide ntified in 1/9444 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs118204456). Please note that for disease s with clinical variability or reduced penetrance, pathogenic variants may be pr esent at a low frequency in the general population. In summary, this variant mee ts our criteria to be classified as pathogenic for HAE 3 in an autosomal dominan t manner based upon segregation studies and low frequency in controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	1	not provided

Last Updated: Jul 29, 2024

ClinVar

Relating variation to medicine