NM_003000.3(SDHB):c.136C>T (p.Arg46Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 26, 2022
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:: RCV000132150.8

Allele description [Variation Report for NM_003000.3(SDHB):c.136C>T (p.Arg46Ter)]

NM_003000.3(SDHB):c.136C>T (p.Arg46Ter)

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.136C>T (p.Arg46Ter)

Other names:

p.R46*:CGA>TGA

HGVS:

NC_000001.11:g.17044825G>A
NG_012340.1:g.14346C>T
NM_003000.3:c.136C>TMANE SELECT
NP_002991.2:p.Arg46Ter
NP_002991.2:p.Arg46Ter
LRG_316t1:c.136C>T
LRG_316:g.14346C>T
LRG_316p1:p.Arg46Ter
NC_000001.10:g.17371320G>A
NM_003000.2:c.136C>T
p.R46*

Protein change:

R46*

Links:

dbSNP: rs74315370

NCBI 1000 Genomes Browser:

rs74315370

Molecular consequence:

NM_003000.3:c.136C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000187222	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 26, 2022)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 12618761, 16317055, 16405730, 16912137, 18419787, 18728283, 19075037, 21909610, 26273102, 27539324, 28944243, 30122763 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000187222

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 26, 2022)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas.

Benn DE, Croxson MS, Tucker K, Bambach CP, Richardson AL, Delbridge L, Pullan PT, Hammond J, Marsh DJ, Robinson BG.

Oncogene. 2003 Mar 6;22(9):1358-64.

PubMed [citation]

PMID:: 12618761

Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.

Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG.

J Clin Endocrinol Metab. 2006 Mar;91(3):827-36. Epub 2005 Nov 29.

PubMed [citation]

PMID:: 16317055

See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV000187222.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The p.R46* pathogenic mutation (also known as c.136C>T), located in coding exon 2 of the SDHB gene, results from a C to T substitution at nucleotide position 136. This changes the amino acid from an arginine to a stop codon within coding exon 2. This mutation has been reported multiple times as a disease-causing mutation in patients with PGL-PCC or renal cell carcinoma (Benn DE et al. Oncogene. 2003 Mar;22:1358-64; Benn DE et al. J. Clin. Endocrinol. Metab. 2006 Mar;91:827-36; Brouwers FM et al. J. Clin. Endocrinol. Metab. 2006 Nov;91:4505-9; Srirangalingam U et al. Clin. Endocrinol. 2008 Oct;69:587-96; Ricketts C et al. J. Natl. Cancer Inst. 2008 Sep;100:1260-2; Ghayee HK et al. Endocr. Relat. Cancer. 2009 Mar;16:291-9; Bayley JP et al. BMC Med. Genet. 2006 Jan;7:1; Mason EF et al. Am. J. Surg. Pathol. 2013 Oct;37:1612-8; Pandit R et al. Eur. J. Endocrinol. 2016 Oct;175(4):311-23; Chew WHW et al. Mol Genet Genomic Med. 2017 Sep;5(5):602-607). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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