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NM_003000.3(SDHB):c.79C>T (p.Arg27Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 6, 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:
RCV000129929.10

Allele description [Variation Report for NM_003000.3(SDHB):c.79C>T (p.Arg27Ter)]

NM_003000.3(SDHB):c.79C>T (p.Arg27Ter)

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.79C>T (p.Arg27Ter)
HGVS:
  • NC_000001.11:g.17044882G>A
  • NG_012340.1:g.14289C>T
  • NM_003000.3:c.79C>TMANE SELECT
  • NP_002991.2:p.Arg27Ter
  • NP_002991.2:p.Arg27Ter
  • LRG_316t1:c.79C>T
  • LRG_316:g.14289C>T
  • LRG_316p1:p.Arg27Ter
  • NC_000001.10:g.17371377G>A
  • NM_003000.2:c.79C>T
  • p.R27*
Protein change:
R27*; ARG27TER
Links:
OMIM: 185470.0006; dbSNP: rs74315369
NCBI 1000 Genomes Browser:
rs74315369
Molecular consequence:
  • NM_003000.3:c.79C>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000184747Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 6, 2023) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

SDHB mutation analysis in familial and sporadic phaeochromocytoma identifies a novel mutation.

Cascón A, Cebrián A, Ruiz-Llorente S, Tellería D, Benítez J, Robledo M.

J Med Genet. 2002 Oct;39(10):E64. No abstract available.

PubMed [citation]
PMID:
12362046
PMCID:
PMC1734998

Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma.

Vanharanta S, Buchta M, McWhinney SR, Virta SK, Peçzkowska M, Morrison CD, Lehtonen R, Januszewicz A, Järvinen H, Juhola M, Mecklin JP, Pukkala E, Herva R, Kiuru M, Nupponen NN, Aaltonen LA, Neumann HP, Eng C.

Am J Hum Genet. 2004 Jan;74(1):153-9. Epub 2003 Dec 18.

PubMed [citation]
PMID:
14685938
PMCID:
PMC1181902
See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000184747.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The p.R27* pathogenic mutation (also known as c.79C>T), located in coding exon 2 of the SDHB gene, results from a C to T substitution at nucleotide position 79. This changes the amino acid from an arginine to a stop codon within coding exon 2. The predicted stop codon occurs within the first 150 nucleotides of SDHB gene. This alteration may escape nonsense-mediated mRNAdecay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653), and it impacts the first 57 amino acids of the protein. However, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This mutation has previously been reported in multiple cases of both sporadic and familial PGL-PCC as well as renal cell carcinoma (Cascón A et al. J. Med. Genet., 2002 Oct;39:E64; Vanharanta S et al. Am. J. Hum. Genet., 2004 Jan;74:153-9; Neumann HP et al. JAMA, 2004 Aug;292:943-51; Naito M et al. Endocrine, 2009 Aug;36:10-5; Graham D et al. Case Rep Genet, 2014 Aug;2014:273423; Casey RT et al. J. Clin. Endocrinol. Metab., 2017 11;102:4013-4022; Fife K et al. BMJ Case Rep, 2017 Aug;2017; Benn DE et al. J. Med. Genet., 2018 11;55:729-734; Albattal S et al. Oncotarget, 2019 Oct;10:5919-5931). Functional studies of this alteration have demonstrated the absence of SDH enzymatic activity as well as the absence of SDHB protein in cell-based assays, indicating nonsense-mediated mRNA decay or protein degradation as a mechanism for absent enzymatic activity (Kim E et al. Endocr. Relat. Cancer, 2015 Jun;22:387-97). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 10, 2024