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NM_003000.3(SDHB):c.137G>T (p.Arg46Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 2, 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:
RCV000571526.6

Allele description [Variation Report for NM_003000.3(SDHB):c.137G>T (p.Arg46Leu)]

NM_003000.3(SDHB):c.137G>T (p.Arg46Leu)

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.137G>T (p.Arg46Leu)
HGVS:
  • NC_000001.11:g.17044824C>A
  • NG_012340.1:g.14347G>T
  • NM_003000.3:c.137G>TMANE SELECT
  • NP_002991.2:p.Arg46Leu
  • NP_002991.2:p.Arg46Leu
  • LRG_316t1:c.137G>T
  • LRG_316:g.14347G>T
  • LRG_316p1:p.Arg46Leu
  • NC_000001.10:g.17371319C>A
  • NM_003000.2:c.137G>T
Protein change:
R46L
Links:
dbSNP: rs772551056
NCBI 1000 Genomes Browser:
rs772551056
Molecular consequence:
  • NM_003000.3:c.137G>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000664561Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 2, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome.

Panizza E, Ercolino T, Mori L, Rapizzi E, Castellano M, Opocher G, Ferrero I, Neumann HP, Mannelli M, Goffrini P.

Hum Mol Genet. 2013 Feb 15;22(4):804-15. doi: 10.1093/hmg/dds487. Epub 2012 Nov 21.

PubMed [citation]
PMID:
23175444

Details of each submission

From Ambry Genetics, SCV000664561.6

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

Description

The p.R46L variant (also known as c.137G>T), located in coding exon 2 of the SDHB gene, results from a G to T substitution at nucleotide position 137. The arginine at codon 46 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHB-related disease (Ambry internal data). This alteration has been reported in a paraganglioma-pheochromocytoma cohort, and authors characterized this alteration as having severely impaired function based on reduced oxidative growth, SDH activity and respiration, as well as increased mtDNA mutability following oxidative stress (Panizza E et al. Hum. Mol. Genet., 2013 Feb;22:804-15). 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 majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024