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NM_003000.3(SDHB):c.141G>A (p.Trp47Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 14, 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:
RCV000474236.7

Allele description [Variation Report for NM_003000.3(SDHB):c.141G>A (p.Trp47Ter)]

NM_003000.3(SDHB):c.141G>A (p.Trp47Ter)

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.141G>A (p.Trp47Ter)
HGVS:
  • NC_000001.11:g.17044820C>T
  • NG_012340.1:g.14351G>A
  • NM_003000.3:c.141G>AMANE SELECT
  • NP_002991.2:p.Trp47Ter
  • NP_002991.2:p.Trp47Ter
  • LRG_316t1:c.141G>A
  • LRG_316:g.14351G>A
  • LRG_316p1:p.Trp47Ter
  • NC_000001.10:g.17371315C>T
  • NM_003000.2:c.141G>A
Protein change:
W47*
Links:
dbSNP: rs1060503762
NCBI 1000 Genomes Browser:
rs1060503762
Molecular consequence:
  • NM_003000.3:c.141G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Gastrointestinal stromal tumor
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 4 (PPGL4)
Synonyms:
CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Pheochromocytoma, extraadrenal and cervical paraganglioma; Paragangliomas, hereditary extraadrenal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310
Name:
Pheochromocytoma
Synonyms:
Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000554009Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 14, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma.

Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE.

BMC Med Genet. 2006 Jan 11;7:1.

PubMed [citation]
PMID:
16405730
PMCID:
PMC1343542

Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.

Srirangalingam U, Walker L, Khoo B, MacDonald F, Gardner D, Wilkin TJ, Skelly RH, George E, Spooner D, Monson JP, Grossman AB, Akker SA, Pollard PJ, Plowman N, Avril N, Berney DM, Burrin JM, Reznek RH, Kumar VK, Maher ER, Chew SL.

Clin Endocrinol (Oxf). 2008 Oct;69(4):587-96. doi: 10.1111/j.1365-2265.2008.03274.x. Epub 2008 Apr 14.

PubMed [citation]
PMID:
18419787
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000554009.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 412474). This premature translational stop signal has been observed in individual(s) with paraganglioma, pheochromocytoma, and renal cell carcinoma (PMID: 16405730, 18419787, 21348866, 29386252). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp47*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024