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NM_003000.2(SDHB):c.268C>T (p.Arg90Ter)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Mar 28, 2019)
Last evaluated:
Mar 8, 2019
Accession:
VCV000012778.4
Variation ID:
12778
Description:
single nucleotide variant
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NM_003000.2(SDHB):c.268C>T (p.Arg90Ter)

Allele ID
27817
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p36.13
Genomic location
1: 17033078 (GRCh38) GRCh38 UCSC
1: 17359573 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.11:g.17033078G>A
NC_000001.10:g.17359573G>A
NM_003000.2:c.268C>T NP_002991.2:p.Arg90Ter nonsense
... more HGVS
Protein change
R90*
Other names
p.R90*:CGA>TGA
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00001
Links
OMIM: 185470.0001
dbSNP: rs74315366
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Jan 21, 2014 RCV000013616.20
Pathogenic 1 criteria provided, single submitter Aug 18, 2011 RCV000030621.1
Pathogenic 2 criteria provided, single submitter Mar 8, 2019 RCV000037718.4
Pathogenic 1 criteria provided, single submitter Jul 23, 2018 RCV000183211.4
Pathogenic 1 criteria provided, single submitter Dec 21, 2017 RCV000215883.3
Pathogenic 1 criteria provided, single submitter Nov 8, 2018 RCV000627749.3
Pathogenic 1 criteria provided, single submitter Oct 31, 2018 RCV000763272.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SDHB Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
479 506

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
pathogenic
(Aug 18, 2011)
criteria provided, single submitter
Method: curation, clinical testing
Pheochromocytoma/Paraganglioma
(autosomal dominant)
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000053299.1
Submitted: (Aug 18, 2011)
Evidence details
Publications
PubMed (2)
Comment:
Converted during submission to Pathogenic.
Pathogenic
(Jan 21, 2014)
criteria provided, single submitter
Method: clinical testing
Paragangliomas 4
(Autosomal dominant inheritance)
Allele origin: unknown
UCLA Clinical Genomics Center, UCLA
Study: CES
Accession: SCV000255462.2
Submitted: (May 14, 2015)
Evidence details
Pathogenic
(Dec 21, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000274572.5
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (9)
Comment:
Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic ... (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Paragangliomas 4
Pheochromocytoma
Paraganglioma and gastric stromal sarcoma
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893916.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Jul 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000235630.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted SDHB c.268C>T at the cDNA level and p.Arg90Ter (R90X) at the protein level. The substitution creates a nonsense variant, which changes ... (more)
Pathogenic
(Nov 08, 2018)
criteria provided, single submitter
Method: clinical testing
Gastrointestinal stroma tumor
Paragangliomas 4
Pheochromocytoma
Allele origin: germline
Invitae
Accession: SCV000554022.5
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (12)
Comment:
This sequence change creates a premature translational stop signal at codon 90 (p.Arg90*) of the SDHB gene. It is expected to result in an absent ... (more)
Pathogenic
(Mar 08, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary Paraganglioma-Pheochromocytoma Syndromes
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000061380.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (14)
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Pathogenic
(Jul 01, 2001)
no assertion criteria provided
Method: literature only
PARAGANGLIOMAS 4
Allele origin: germline
OMIM
Accession: SCV000033863.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
Pathogenic
(-)
no assertion criteria provided
Method: research
Hereditary Paraganglioma-Pheochromocytoma Syndromes
Allele origin: germline
Section on Medical Neuroendocrinolgy,National Institutes of Health
Accession: SCV000599490.1
Submitted: (Jul 10, 2017)
Evidence details

Citations for this variant

Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations. Jochmanova I Journal of cancer research and clinical oncology 2017 PMID: 28374168
A Duodenal SDH-Deficient Gastrointestinal Stromal Tumor in a Patient With a Germline SDHB Mutation. Elston MS The Journal of clinical endocrinology and metabolism 2017 PMID: 28324028
Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers. Eijkelenkamp K Familial cancer 2017 PMID: 27573198
Attention Deficit Hyperactivity Disorder in Pediatric Patients with Pheochromocytoma and Paraganglioma. Batsis M Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2016 PMID: 27171833
Structural and functional consequences of succinate dehydrogenase subunit B mutations. Kim E Endocrine-related cancer 2015 PMID: 25972245
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Clinical exome sequencing for genetic identification of rare Mendelian disorders. Lee H JAMA 2014 PMID: 25326637
Integrative genetic characterization and phenotype correlations in pheochromocytoma and paraganglioma tumours. Crona J PloS one 2014 PMID: 24466223
Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer. Ricketts CJ The Journal of urology 2012 PMID: 23083876
High prevalence of founder mutations of the succinate dehydrogenase genes in the Netherlands. Hensen EF Clinical genetics 2012 PMID: 21348866
Renal tumors associated with germline SDHB mutation show distinctive morphology. Gill AJ The American journal of surgical pathology 2011 PMID: 21934479
[The mutations of germline succinate dehydrogrnase subunit B (SDHB) in sporadic paragangliomas]. Zu TJ Shanghai kou qiang yi xue = Shanghai journal of stomatology 2011 PMID: 21909610
The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. Burnichon N The Journal of clinical endocrinology and metabolism 2009 PMID: 19454582
Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers. Srirangalingam U Clinical endocrinology 2008 PMID: 18419787
Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas. Klein RD Diagnostic molecular pathology : the American journal of surgical pathology, part B 2008 PMID: 18382370
Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. Amar L The Journal of clinical endocrinology and metabolism 2007 PMID: 17652212
The occurrence of SDHB gene mutations in pheochromocytoma. Van Nederveen FH Annals of the New York Academy of Sciences 2006 PMID: 17102084
Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. Benn DE The Journal of clinical endocrinology and metabolism 2006 PMID: 16317055
Genetic testing in pheochromocytoma or functional paraganglioma. Amar L Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005 PMID: 16314641
New insights in the genetics of adrenocortical tumors, pheochromocytomas and paragangliomas. Bertherat J Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2005 PMID: 16001332
Mutations of the SDHB and SDHD genes. Pawlu C Familial cancer 2005 PMID: 15883710
A thyroid nodule revealing a paraganglioma in a patient with a new germline mutation in the succinate dehydrogenase B gene. Zantour B European journal of endocrinology 2004 PMID: 15476441
A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas. Maier-Woelfle M The Journal of clinical endocrinology and metabolism 2004 PMID: 14715873
On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Baysal BE Trends in endocrinology and metabolism: TEM 2003 PMID: 14643060
Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas. Benn DE Oncogene 2003 PMID: 12618761
Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. Gimenez-Roqueplo AP The Journal of clinical endocrinology and metabolism 2002 PMID: 12364472
The pressure rises: update on the genetics of phaeochromocytoma. Maher ER Human molecular genetics 2002 PMID: 12351569
Hereditary paraganglioma targets diverse paraganglia. Baysal BE Journal of medical genetics 2002 PMID: 12205103
Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Astuti D American journal of human genetics 2001 PMID: 11404820
A family with hereditary extra-adrenal paragangliomas without evidence for mutations in the von Hippel-Lindau disease or ret genes. Sk├Âldberg F Clinical endocrinology 1998 PMID: 9509062
- - - - PMID: 163114641

Record last updated Oct 11, 2019