NM_003000.3(SDHB):c.654G>A (p.Trp218Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2022
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:: RCV000492179.3

Allele description [Variation Report for NM_003000.3(SDHB):c.654G>A (p.Trp218Ter)]

NM_003000.3(SDHB):c.654G>A (p.Trp218Ter)

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.654G>A (p.Trp218Ter)

HGVS:

NC_000001.11:g.17022719C>T
NG_012340.1:g.36452G>A
NM_003000.3:c.654G>AMANE SELECT
NP_002991.2:p.Trp218Ter
NP_002991.2:p.Trp218Ter
LRG_316t1:c.654G>A
LRG_316:g.36452G>A
LRG_316p1:p.Trp218Ter
NC_000001.10:g.17349214C>T
NM_003000.2:c.654G>A

Protein change:

W218*

Links:

dbSNP: rs916516745

NCBI 1000 Genomes Browser:

rs916516745

Molecular consequence:

NM_003000.3:c.654G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000581200	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19454582, 27279923, 27573198 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000581200

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 14, 2022)

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

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP; PGL.NET network..

J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub 2009 May 19.

PubMed [citation]

PMID:: 19454582

Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients.

Bennedbæk M, Rossing M, Rasmussen ÅK, Gerdes AM, Skytte AB, Jensen UB, Nielsen FC, Hansen TVO.

Hered Cancer Clin Pract. 2016;14:13. doi: 10.1186/s13053-016-0053-6.

PubMed [citation]

PMID:: 27279923
PMCID:: PMC4898401

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000581200.6

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

Description

The p.W218* pathogenic mutation (also known as c.654G>A), located in coding exon 7 of the SDHB gene, results from a G to A substitution at nucleotide position 654. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. This mutation has been detected in multiple individuals with a paraganglioma (Burnichon N et al. J Clin Endocrinol Metab, 2009 Aug;94:2817-27; Eijkelenkamp K et al. Fam Cancer, 2017 01;16:123-130; Bennedbæk M et al. Hered Cancer Clin Pract, 2016 Jun;14:13; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 12, 2024

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