NM_003000.3(SDHB):c.689G>T (p.Arg230Leu) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jul 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000473831.6

Allele description [Variation Report for NM_003000.3(SDHB):c.689G>T (p.Arg230Leu)]

NM_003000.3(SDHB):c.689G>T (p.Arg230Leu)

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.689G>T (p.Arg230Leu)
HGVS:
  • NC_000001.11:g.17022684C>A
  • NG_012340.1:g.36487G>T
  • NM_003000.2:c.689G>T
  • NM_003000.3:c.689G>TMANE SELECT
  • NP_002991.2:p.Arg230Leu
  • NP_002991.2:p.Arg230Leu
  • LRG_316t1:c.689G>T
  • LRG_316:g.36487G>T
  • LRG_316p1:p.Arg230Leu
  • NC_000001.10:g.17349179C>A
  • NC_000001.10:g.17349179C>A
  • p.R230L
Protein change:
R230L
Links:
dbSNP: rs587782604
NCBI 1000 Genomes Browser:
rs587782604
Molecular consequence:
  • NM_003000.2:c.689G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003000.3:c.689G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000554032Invitaecriteria provided, single submitter
Pathogenic
(Jul 24, 2020)
germlineclinical testing

PubMed (9)
[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

Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas.

Klein RD, Jin L, Rumilla K, Young WF Jr, Lloyd RV.

Diagn Mol Pathol. 2008 Jun;17(2):94-100. doi: 10.1097/PDM.0b013e318150d67c.

PubMed [citation]
PMID:
18382370

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, et al.

Cancer Res. 2009 Apr 15;69(8):3650-6. doi: 10.1158/0008-5472.CAN-08-4057. Epub 2009 Apr 7.

PubMed [citation]
PMID:
19351833
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000554032.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces arginine with leucine at codon 230 of the SDHB protein (p.Arg230Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with paraganglioma (PMID: 18382370, 19351833, 27539324, 23934599). ClinVar contains an entry for this variant (Variation ID: 184933). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The p.Arg230 amino acid residue in SDHB has been determined to be clinically significant (PMID: 25405498, 20592014, 26259135, 16912137). This suggests that variants that disrupt this residue are likely to be causative of disease. 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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