NM_003002.4(SDHD):c.129G>A (p.Trp43Ter) AND Paragangliomas 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 29, 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:: RCV000007322.17

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:: Paragangliomas 1
Synonyms:: Paragangliomata; Glomus tumors familial 1; Paraganglioma - glomus jugulare; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008192; MedGen: C3494181; Orphanet: 29072; OMIM: 168000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027520	OMIM	no assertion criteria provided	Pathogenic (May 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 12111639, 18211978
SCV004019079	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Mar 29, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000027520

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2008)

germline

literature only

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

SCV004019079

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Mar 29, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

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

Paraganglioma after maternal transmission of a succinate dehydrogenase gene mutation.

Pigny P, Vincent A, Cardot Bauters C, Bertrand M, de Montpreville VT, Crepin M, Porchet N, Caron P.

J Clin Endocrinol Metab. 2008 May;93(5):1609-15. doi: 10.1210/jc.2007-1989. Epub 2008 Jan 22.

PubMed [citation]

PMID:: 18211978

Details of each submission

From OMIM, SCV000027520.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a patient with paragangliomas and a family history of pheochromocytoma (PPGL1; 168000), Cascon et al. (2002) identified a heterozygous c.129G-A transition in exon 2 of the SDHD gene, resulting in a trp43-to-ter (W43X) substitution and a truncated protein of 43 amino acids.

Pigny et al. (2008) reported a family with maternal transmission of the W43X mutation in the third generation. A boy received the mutation from his mother and developed a glomus tympanicum paraganglioma at 11 years of age. He shared only the 11q23 haplotype with the other affected members of the family. Methylation analysis of the differentially methylated region upstream of the maternally expressed H19 gene, mapped to 11p15, showed that the seventh CTCF binding site was hypermethylated in the germline of the affected boy, suggesting a gain of imprinting. The authors concluded that maternal transmission of a SDHD-linked paraganglioma, even if a rare event, can occur. The authors proposed that children who inherit a pathogenic mutation from their mother should be considered at risk for paraganglioma.

#	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		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004019079.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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

Last Updated: May 26, 2024

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