NM_003000.3(SDHB):c.137G>A (p.Arg46Gln) AND SDHB-related disorder

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 1, 2017
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:: RCV000722045.4

Allele description [Variation Report for NM_003000.3(SDHB):c.137G>A (p.Arg46Gln)]

NM_003000.3(SDHB):c.137G>A (p.Arg46Gln)

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>A (p.Arg46Gln)

Other names:

p.R46Q:CGA>CAA

HGVS:

NC_000001.11:g.17044824C>T
NG_012340.1:g.14347G>A
NM_003000.3:c.137G>AMANE SELECT
NP_002991.2:p.Arg46Gln
NP_002991.2:p.Arg46Gln
LRG_316t1:c.137G>A
LRG_316:g.14347G>A
LRG_316p1:p.Arg46Gln
NC_000001.10:g.17371319C>T
NM_003000.2:c.137G>A
P21912:p.Arg46Gln
p.R46Q

Protein change:

R46Q

Links:

UniProtKB: P21912#VAR_054377; dbSNP: rs772551056

NCBI 1000 Genomes Browser:

rs772551056

Molecular consequence:

NM_003000.3:c.137G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: SDHB-related disorder
Synonyms:: SDHB-Related Disorders; SDHB-related condition
Identifiers:: MedGen: CN239418

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000853087	Snyder Lab, Genetics Department, Stanford University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 1, 2017)	germline	research	PubMed (8) [See all records that cite these PMIDs] 26719882, 12364472, 25972245, 24659481, 24102379, 19802898, 12618761, 25741868
SCV005358433	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Jul 19, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000853087

Snyder Lab, Genetics Department, Stanford University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 1, 2017)

germline

research

PubMed (8)
[See all records that cite these PMIDs]

SCV005358433

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Jul 19, 2024)

germline

clinical testing

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, research

Citations

PubMed

SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery.

Saxena N, Maio N, Crooks DR, Ricketts CJ, Yang Y, Wei MH, Fan TW, Lane AN, Sourbier C, Singh A, Killian JK, Meltzer PS, Vocke CD, Rouault TA, Linehan WM.

J Natl Cancer Inst. 2016 Jan;108(1). doi: 10.1093/jnci/djv287.

PubMed [citation]

PMID:: 26719882
PMCID:: PMC4732025

Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma.

Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rötig A, Jeunemaitre X.

J Clin Endocrinol Metab. 2002 Oct;87(10):4771-4.

PubMed [citation]

PMID:: 12364472

See all PubMed Citations (8)

Details of each submission

From Snyder Lab, Genetics Department, Stanford University, SCV000853087.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (8)

#	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

From PreventionGenetics, part of Exact Sciences, SCV005358433.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The SDHB c.137G>A variant is predicted to result in the amino acid substitution p.Arg46Gln. This variant has been reported in several unrelated individuals with pheochromocytoma, paraganglioma, and gastrointestinal stromal tumors (see for example, Gimenez-Roqueplo et al. 2002. PubMed ID: 12364472; Gimenez-Roqueplo et al. 2003. PubMed ID: 14500403 Benn et al. 2003. PubMed ID: 12618761; Neumann et al. 2004. PubMed ID: 15328326; Miettinen et al. 2013. PubMed ID: 23282968). Functional in vitro assays show that this variant leads to protein instability (Yang et al. 2012. PubMed ID: 22835832; Saxena et al. 2016. PubMed ID: 26719882). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, it is reported as likely pathogenic/pathogenic by several laboratories (https://www.ncbi.nlm.nih.gov/clinvar/variation/183793/). We classify this variant as pathogenic.

#	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: Oct 20, 2024

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