NM_003000.3(SDHB):c.653G>A (p.Trp218Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Oct 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000822698.1

Allele description [Variation Report for NM_003000.3(SDHB):c.653G>A (p.Trp218Ter)]

NM_003000.3(SDHB):c.653G>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.653G>A (p.Trp218Ter)
HGVS:
  • NC_000001.11:g.17022720C>T
  • NG_012340.1:g.36451G>A
  • NM_003000.2:c.653G>A
  • NM_003000.3:c.653G>AMANE SELECT
  • NP_002991.2:p.Trp218Ter
  • NP_002991.2:p.Trp218Ter
  • LRG_316t1:c.653G>A
  • LRG_316:g.36451G>A
  • LRG_316p1:p.Trp218Ter
  • NC_000001.10:g.17349215C>T
Protein change:
W218*
Links:
dbSNP: rs1553177290
NCBI 1000 Genomes Browser:
rs1553177290
Molecular consequence:
  • NM_003000.2:c.653G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003000.3:c.653G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Gastrointestinal stromal tumor (GIST)
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 4 (PGL4)
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000963511Invitaecriteria provided, single submitter
Pathogenic
(Oct 24, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000963511.1

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

Description

This sequence change creates a premature translational stop signal (p.Trp218*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with paraganglioma-pheochromocytoma syndromes (PMID: 22517554, 27573198, 27279923). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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