NM_003000.3(SDHB):c.688C>T (p.Arg230Cys) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Aug 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000528137.6

Allele description [Variation Report for NM_003000.3(SDHB):c.688C>T (p.Arg230Cys)]

NM_003000.3(SDHB):c.688C>T (p.Arg230Cys)

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.688C>T (p.Arg230Cys)
HGVS:
  • NC_000001.11:g.17022685G>A
  • NG_012340.1:g.36486C>T
  • NM_003000.2:c.688C>T
  • NM_003000.3:c.688C>TMANE SELECT
  • NP_002991.2:p.Arg230Cys
  • NP_002991.2:p.Arg230Cys
  • LRG_316t1:c.688C>T
  • LRG_316:g.36486C>T
  • LRG_316p1:p.Arg230Cys
  • NC_000001.10:g.17349180G>A
  • P21912:p.Arg230Cys
  • p.R230C
Protein change:
R230C
Links:
UniProtKB: P21912#VAR_054383; dbSNP: rs138996609
NCBI 1000 Genomes Browser:
rs138996609
Molecular consequence:
  • NM_003000.2:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003000.3:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gastrointestinal stroma tumor (GIST)
Synonyms:
Gastrointestinal stromal tumor; Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic
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
SCV000644765Invitaecriteria provided, single submitter
Pathogenic
(Aug 14, 2020)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.

Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X; COMETE Network..

Cancer Res. 2003 Sep 1;63(17):5615-21.

PubMed [citation]
PMID:
14500403

Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas.

Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, Bertagna X, Schlumberger M, Jeunemaitre X, Gimenez-Roqueplo AP, Plouin PF.

J Clin Endocrinol Metab. 2007 Oct;92(10):3822-8. Epub 2007 Jul 24.

PubMed [citation]
PMID:
17652212
See all PubMed Citations (11)

Details of each submission

From Invitae, SCV000644765.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces arginine with cysteine at codon 230 of the SDHB protein (p.Arg230Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs138996609, ExAC 0.002%). This variant has been reported in several individuals affected with malignant or non-malignant pheochromocytoma or paraganglioma (PMID: 14500403, 17652212, 25873086, 19454582, 20208144, 22517554). ClinVar contains an entry for this variant (Variation ID: 185077). Experimental studies have shown that this missense change results in reduced SDHB protein stability (PMID: 22835832). Two other missense substitutions at this codon (p.Arg230His and p.Arg230Leu) have been determined to be pathogenic (PMID: 18382370, 19351833, 23934599, Invitae). This suggests that the arginine residue is critical for SDHB protein function and that other missense substitutions at this position may also be pathogenic. 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: Nov 20, 2021

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