NM_003002.4(SDHD):c.129G>A (p.Trp43Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 2018
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:: RCV000222413.10

Allele description [Variation Report for NM_003002.4(SDHD):c.129G>A (p.Trp43Ter)]

NM_003002.4(SDHD):c.129G>A (p.Trp43Ter)

Gene:

SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_003002.4(SDHD):c.129G>A (p.Trp43Ter)

HGVS:

NC_000011.10:g.112087933G>A
NG_012337.3:g.6087G>A
NG_033145.1:g.3866C>T
NM_001276503.2:c.129G>A
NM_001276504.2:c.53-934G>A
NM_001276506.2:c.129G>A
NM_003002.4:c.129G>AMANE SELECT
NP_001263432.1:p.Trp43Ter
NP_001263435.1:p.Trp43Ter
NP_002993.1:p.Trp43Ter
LRG_9t1:c.129G>A
LRG_9:g.6087G>A
LRG_9p1:p.Trp43Ter
NC_000011.9:g.111958657G>A
NM_001276506.1:c.129G>A
NM_003002.2:c.129G>A
NM_003002.3:c.129G>A
NR_077060.2:n.164G>A
p.Trp43*

Protein change:

W43*; TRP43TER

Links:

OMIM: 602690.0023; dbSNP: rs104894308

NCBI 1000 Genomes Browser:

rs104894308

Molecular consequence:

NM_001276504.2:c.53-934G>A - intron variant - [Sequence Ontology: SO:0001627]
NR_077060.2:n.164G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001276503.2:c.129G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001276506.2:c.129G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003002.4:c.129G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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
SCV000276168	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 6, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12111639, 17973943, 18561749 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276168

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 6, 2018)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma.

Cascon A, Ruiz-Llorente S, Cebrian A, Telleria D, Rivero JC, Diez JJ, Lopez-Ibarra PJ, Jaunsolo MA, Benitez J, Robledo M.

Eur J Hum Genet. 2002 Aug;10(8):457-61.

PubMed [citation]

PMID:: 12111639

Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.

Timmers HJ, Pacak K, Bertherat J, Lenders JW, Duet M, Eisenhofer G, Stratakis CA, Niccoli-Sire P, Tran BH, Burnichon N, Gimenez-Roqueplo AP.

Clin Endocrinol (Oxf). 2008 Apr;68(4):561-6. Epub 2007 Oct 31.

PubMed [citation]

PMID:: 17973943

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000276168.8

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

Description

The p.W43* pathogenic mutation (also known as c.129G>A) located in coding exon 2 of the SDHD gene, results from a G to A substitution at nucleotide position 129. This changes the amino acid from a tryptophan to a stop codon within coding exon 2. This pathogenic mutation has been identified in a patient with multiple paragangliomas (PGLs) and a family history of pheochromocytoma, and it has been predicted to lead to a protein that lacks the transmembrane, signal, and heme-binding domains (Cascon A et al. Eur. J. Hum. Genet. 2002 Aug; 10(8):457-61). The p.W43* pathogenic mutation has also been reported in a French female diagnosed with metastatic bilateral cartoid HNPGLs at age 22 who had no family history of PGLs (Timmers HJ et al. Clin. Endocrinol. (Oxf). 2008 Apr;68:561-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 26, 2024

ClinVar

Relating variation to medicine