NM_003000.3(SDHB):c.724C>T (p.Arg242Cys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 2, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000166478.2

Allele description [Variation Report for NM_003000.3(SDHB):c.724C>T (p.Arg242Cys)]

NM_003000.3(SDHB):c.724C>T (p.Arg242Cys)

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.724C>T (p.Arg242Cys)
HGVS:
  • NC_000001.11:g.17022649G>A
  • NG_012340.1:g.36522C>T
  • NM_003000.2:c.724C>T
  • NM_003000.3:c.724C>TMANE SELECT
  • NP_002991.2:p.Arg242Cys
  • NP_002991.2:p.Arg242Cys
  • LRG_316t1:c.724C>T
  • LRG_316:g.36522C>T
  • LRG_316p1:p.Arg242Cys
  • NC_000001.10:g.17349144G>A
  • NC_000001.10:g.17349144G>A
  • p.R242C
Protein change:
R242C
Links:
dbSNP: rs786203251
NCBI 1000 Genomes Browser:
rs786203251
Molecular consequence:
  • NM_003000.2:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003000.3:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000217276Ambry Geneticscriteria provided, single submitter
Pathogenic
(Jan 2, 2019)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features.

Badenhop RF, Jansen JC, Fagan PA, Lord RS, Wang ZG, Foster WJ, Schofield PR.

J Med Genet. 2004 Jul;41(7):e99. No abstract available.

PubMed [citation]
PMID:
15235042
PMCID:
PMC1735850

Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas.

Schiavi F, Savvoukidis T, Trabalzini F, Grego F, Piazza M, Amistà P, Demattè S, Del Piano A, Cecchini ME, Erlic Z, De Lazzari P, Mantero F, Opocher G.

Ann N Y Acad Sci. 2006 Aug;1073:190-7.

PubMed [citation]
PMID:
17102086
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000217276.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (9)

Description

The p.R242C pathogenic mutation (also known as c.724C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at nucleotide position 724. The arginine at codon 242 is replaced by cysteine, an amino acid with highly dissimilar properties. <span style="background-color:initial">This alteration has been identified in numerous individuals with sporadic and familial paragangliomas/pheochromocytomas (Jafri M et al. Clin. Endocrinol. (Oxf). 2013 Jun;78(6):898-906; <span style="background-color:initial">Lefebvre S et al. Horm. Metab. Res. 2012 May;44(5):334-8; Badenhop RF et al. J. Med. Genet. 2004 Jul;41(7):e99; Schiavi F et al. Ann. N. Y. Acad. Sci. 2006 Aug;1073:190-7; Burnichon N et al. J. Clin. Endocrinol. Metab. 2009 Aug; 94(8):2817-27; Andrews KA et al. J. Med. Genet. 2018 Jun;55(6):384-394<span style="background-color:initial">). A functional study utilizing a yeast growth assay classified this alteration as a "mildly impaired mutation" after finding that analogous yeast p.R242C mutants were able to partially rescue oxidative cell growth but had significantly decreased SDH enzyme activity (<span style="background-color:initial">Panizza E et al. Hum. Mol. Genet. 2013 Feb; 22(4):804-15)<span style="background-color:initial">. <span style="background-color:initial">This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2021

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