VCV000185077.18 - ClinVar

NM_003000.3(SDHB):c.688C>T (p.Arg230Cys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003000.3(SDHB):c.688C>T (p.Arg230Cys)

Variation ID: 185077 Accession: VCV000185077.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p36.13 1: 17022685 (GRCh38) [ NCBI UCSC ] 1: 17349180 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 24, 2015	May 1, 2024	Dec 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_003000.3:c.688C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002991.2:p.Arg230Cys	missense
NC_000001.11:g.17022685G>A
NC_000001.10:g.17349180G>A
NG_012340.1:g.36486C>T
LRG_316:g.36486C>T
LRG_316t1:c.688C>T	LRG_316p1:p.Arg230Cys
	P21912:p.Arg230Cys

... more HGVS ... less HGVS

Protein change

R230C

Other names

Canonical SPDI

NC_000001.11:17022684:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA016074 UniProtKB: P21912#VAR_054383 dbSNP: rs138996609 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SDHB		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	1329	1447

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Nov 22, 2022	RCV000164435.5
Hereditary pheochromocytoma-paraganglioma	Pathogenic (2)	criteria provided, single submitter	Aug 8, 2023	RCV000505374.4
not provided	Pathogenic (1)	criteria provided, single submitter	Oct 5, 2017	RCV000520697.2
Gastrointestinal stromal tumor Paragangliomas 4 Pheochromocytoma	Pathogenic (1)	criteria provided, single submitter	Dec 1, 2023	RCV000528137.10
Paragangliomas 4	Pathogenic/Likely pathogenic (4)	criteria provided, multiple submitters, no conflicts	Feb 8, 2023	RCV000660258.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paragangliomas 4 Affected status: yes Allele origin: germline	Center for Human Genetics, Inc, Center for Human Genetics, Inc Accession: SCV000782279.1 First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018
Pathogenic (Jan 14, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paragangliomas 4 Affected status: unknown Allele origin: germline	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine Accession: SCV000840068.1 First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018	Comment: The c.688C>T (p.Arg230Cys) variant in the SDHB gene has been reported in several unrelated individuals with pheochromocytoma or paraganglioma (PMID: 14500403, 24939699, 20208144, and 28374168). … (more) The c.688C>T (p.Arg230Cys) variant in the SDHB gene has been reported in several unrelated individuals with pheochromocytoma or paraganglioma (PMID: 14500403, 24939699, 20208144, and 28374168). Functional assays have demonstrated that this missense change results in an unstable protein, and in the tumor of an individual with this variant complete and selective loss of mitochondrial complex II enzyme activity was observed (PMID: 22835832, 14500403). Additionally, two other pathogenic/likely pathogenic missense substitutions at this codon have been reported (PMID: 22835832, 23934599, 18382370, and 19351833,) suggesting that the Arg230 residue is critical for normal functioning of the SDHB protein. In light of the currently available data this variant in the SDHB gene is classified pathogenic. (less)
Pathogenic (Oct 05, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000617569.1 First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017	Comment: This pathogenic variant is denoted SDHB c.688C>T at the cDNA level, p.Arg230Cys (R230C) at theprotein level, and results in the change of an Arginine to … (more) This pathogenic variant is denoted SDHB c.688C>T at the cDNA level, p.Arg230Cys (R230C) at theprotein level, and results in the change of an Arginine to a Cysteine (CGC>TGC). This variant was observed in severalindividuals with pheochromocytoma or paraganglioma (Gimenez-Roqueplo 2003, Lefebvre 2012, Hermsen 2010,Janssen, Jochmanova 2017). In addition, functional assays have demonstrated this variant to result in an unstableprotein, and in the tumor of an individual harboring this variant, complete and selective loss of mitochondrial complex IIenzyme activity was observed (Yang 2012, Gimenez-Roqueplo 2003). SDHB Arg230Cys was not observed at asignificant allele frequency in large population cohorts (Lek 2016). Since Arginine and Cysteine differ in polarity,charge, size or other properties, this is considered a non-conservative amino acid substitution. SDHB Arg230Cysoccurs at a position that is conserved across species and is not located in a known functional domain. In silicoanalyses predict that this pathogenic variant is probably damaging to protein structure and function. Based on currentlyavailable evidence, we consider this variant to be pathogenic (less)
Likely pathogenic (Feb 08, 2023)	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) Method: clinical testing	Paragangliomas 4 Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV004017902.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Publications: PubMed (4) PubMed: 14500403‚ 33362715‚ 28374168‚ 34906457 Comment: This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 14500403, 33362715, 28374168, 34906457]. … (more) This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 14500403, 33362715, 28374168, 34906457]. This variant is expected to disrupt protein structure [Myriad internal data]. (less)
Pathogenic (Dec 01, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Gastrointestinal stromal tumor Paragangliomas 4 Pheochromocytoma Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000644765.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024	Publications: PubMed (11) PubMed: 28492532‚ 14500403‚ 17652212‚ 19454582‚ 20208144‚ 22517554‚ 25873086‚ 22835832‚ 18382370‚ 19351833‚ 23934599 Comment: This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 230 of the SDHB protein … (more) This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 230 of the SDHB protein (p.Arg230Cys). This variant is present in population databases (rs138996609, gnomAD 0.0009%). This missense change has been observed in individuals with malignant or non-malignant pheochromocytoma or paraganglioma (PMID: 14500403, 17652212, 19454582, 20208144, 22517554, 25873086). ClinVar contains an entry for this variant (Variation ID: 185077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SDHB function (PMID: 22835832). This variant disrupts the p.Arg230 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18382370, 19351833, 23934599; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Nov 22, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000215074.9 First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024	Publications: PubMed (8) PubMed: 14500403‚ 16103922‚ 17652212‚ 19351833‚ 19393419‚ 19454582‚ 22835832‚ 29386252 Comment: The p.R230C pathogenic mutation (also known as c.688C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at … (more) The p.R230C pathogenic mutation (also known as c.688C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at nucleotide position 688. The arginine at codon 230 is replaced by cysteine, an amino acid with highly dissimilar properties. This pathogenic variant has been reported in numerous individuals diagnosed with pheochromocytomas and/or paragangliomas (Gimenez-Roqueplo AP et al. Cancer Res. 2003 Sep 1;63(17):5615-21; Dahia PL et al. PLoS Genet. 2005 Jul;1(1):72-80; Neumann HP et al. Cancer Res. 2009 Apr 15;69(8):3650-6; Sevilla MA et al. Otolaryngol Head Neck Surg. 2009 May;140(5):724-9; Burnichon N et al. J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27; Yang C et al. FASEB J. 2012 Nov;26(11):4506-16; Andrews KA et al. J. Med. Genet. 2018 Jun;55:384-394). Additionally, two disease-causing variants, p.R230H and p.R230L, have been described in the same codon. 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. (less)
Pathogenic (Jan 06, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Paragangliomas 4 Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001369396.2 First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PP3.
Pathogenic (Aug 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary pheochromocytoma-paraganglioma (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004821938.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Publications: PubMed (15) PubMed: 14500403‚ 16103922‚ 17652212‚ 19351833‚ 19454582‚ 20208144‚ 22517554‚ 22835832‚ 25873086‚ 29386252‚ 30536464‚ 33420946‚ 34906457‚ 35673401‚ 35904169 Comment: This missense variant replaces arginine with cysteine at codon 230 of the SDHB protein. Computational prediction suggests that this variant may have deleterious impact on … (more) This missense variant replaces arginine with cysteine at codon 230 of the SDHB protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant may impact protein stability and increase SDHB ubiquitination (PMID: 14500403, 22835832, 35673401). This variant has been reported in individuals affected with pheochromocytomas, paragangliomas, and gastrointestinal stromal tumors (PMID: 16103922, 17652212, 19351833, 19454582, 20208144, 22517554, 25873086, 29386252, 30536464, 34906457, 33420946, 35673401, 35904169). Other amino acid changes at this codon are considered disease causing (R230L, R230H, R230G; ClinVar Variant IDs: 184933, 142637, 1755980). This variant has been identified in 2/251398 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less) Number of individuals with the variant: 1 Zygosity: Single Heterozygote
Pathogenic (-)	no assertion criteria provided Method: research	Hereditary pheochromocytoma-paraganglioma Affected status: yes Allele origin: germline	Section on Medical Neuroendocrinolgy, National Institutes of Health Accession: SCV000599523.1 First in ClinVar: Sep 15, 2017 Last updated: Sep 15, 2017

Comment:

The c.688C>T (p.Arg230Cys) variant in the SDHB gene has been reported in several unrelated individuals with pheochromocytoma or paraganglioma (PMID: 14500403, 24939699, 20208144, and 28374168). Functional assays have demonstrated that this missense change results in an unstable protein, and in the tumor of an individual with this variant complete and selective loss of mitochondrial complex II enzyme activity was observed (PMID: 22835832, 14500403). Additionally, two other pathogenic/likely pathogenic missense substitutions at this codon have been reported (PMID: 22835832, 23934599, 18382370, and 19351833,) suggesting that the Arg230 residue is critical for normal functioning of the SDHB protein. In light of the currently available data this variant in the SDHB gene is classified pathogenic.

Comment:

This pathogenic variant is denoted SDHB c.688C>T at the cDNA level, p.Arg230Cys (R230C) at theprotein level, and results in the change of an Arginine to a Cysteine (CGC>TGC). This variant was observed in severalindividuals with pheochromocytoma or paraganglioma (Gimenez-Roqueplo 2003, Lefebvre 2012, Hermsen 2010,Janssen, Jochmanova 2017). In addition, functional assays have demonstrated this variant to result in an unstableprotein, and in the tumor of an individual harboring this variant, complete and selective loss of mitochondrial complex IIenzyme activity was observed (Yang 2012, Gimenez-Roqueplo 2003). SDHB Arg230Cys was not observed at asignificant allele frequency in large population cohorts (Lek 2016). Since Arginine and Cysteine differ in polarity,charge, size or other properties, this is considered a non-conservative amino acid substitution. SDHB Arg230Cysoccurs at a position that is conserved across species and is not located in a known functional domain. In silicoanalyses predict that this pathogenic variant is probably damaging to protein structure and function. Based on currentlyavailable evidence, we consider this variant to be pathogenic

Comment:

This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 14500403, 33362715, 28374168, 34906457]. This variant is expected to disrupt protein structure [Myriad internal data].

Comment:

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 230 of the SDHB protein (p.Arg230Cys). This variant is present in population databases (rs138996609, gnomAD 0.0009%). This missense change has been observed in individuals with malignant or non-malignant pheochromocytoma or paraganglioma (PMID: 14500403, 17652212, 19454582, 20208144, 22517554, 25873086). ClinVar contains an entry for this variant (Variation ID: 185077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SDHB function (PMID: 22835832). This variant disrupts the p.Arg230 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18382370, 19351833, 23934599; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

Comment:

The p.R230C pathogenic mutation (also known as c.688C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at nucleotide position 688. The arginine at codon 230 is replaced by cysteine, an amino acid with highly dissimilar properties. This pathogenic variant has been reported in numerous individuals diagnosed with pheochromocytomas and/or paragangliomas (Gimenez-Roqueplo AP et al. Cancer Res. 2003 Sep 1;63(17):5615-21; Dahia PL et al. PLoS Genet. 2005 Jul;1(1):72-80; Neumann HP et al. Cancer Res. 2009 Apr 15;69(8):3650-6; Sevilla MA et al. Otolaryngol Head Neck Surg. 2009 May;140(5):724-9; Burnichon N et al. J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27; Yang C et al. FASEB J. 2012 Nov;26(11):4506-16; Andrews KA et al. J. Med. Genet. 2018 Jun;55:384-394). Additionally, two disease-causing variants, p.R230H and p.R230L, have been described in the same codon. 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.

Comment:

This missense variant replaces arginine with cysteine at codon 230 of the SDHB protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant may impact protein stability and increase SDHB ubiquitination (PMID: 14500403, 22835832, 35673401). This variant has been reported in individuals affected with pheochromocytomas, paragangliomas, and gastrointestinal stromal tumors (PMID: 16103922, 17652212, 19351833, 19454582, 20208144, 22517554, 25873086, 29386252, 30536464, 34906457, 33420946, 35673401, 35904169). Other amino acid changes at this codon are considered disease causing (R230L, R230H, R230G; ClinVar Variant IDs: 184933, 142637, 1755980). This variant has been identified in 2/251398 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Correlation of treatment outcome in sanger/RT‑qPCR KIT/PDGFRA wild‑type metastatic gastrointestinal stromal tumors with next‑generation sequencing results: A single‑center report.	Unk M	Oncology reports	2022	PMID: 35904169
Papillary Thyroid Cancer and a TERT Promotor Mutation-positive Paraganglioma in a Patient With a Germline SDHB Mutation.	Alzahrani AS	Journal of the Endocrine Society	2022	PMID: 35673401
Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.	Garrett A	Genetics in medicine : official journal of the American College of Medical Genetics	2022	PMID: 34906457
SDHB large deletions are associated with absence of MIBG uptake in metastatic lesions of malignant paragangliomas.	Petenuci J	Endocrine	2021	PMID: 33420946
Genetic and Clinical Profiles of Pheochromocytoma and Paraganglioma: A Single Center Study.	Ma X	Frontiers in endocrinology	2020	PMID: 33362715
Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma.	Muth A	Journal of internal medicine	2019	PMID: 30536464
Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.	Andrews KA	Journal of medical genetics	2018	PMID: 29386252
SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations.	Jochmanova I	Journal of cancer research and clinical oncology	2017	PMID: 28374168
Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma.	Janssen I	Clinical cancer research : an official journal of the American Association for Cancer Research	2015	PMID: 25873086
Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families.	Jasperson KW	Familial cancer	2014	PMID: 23934599
Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function.	Yang C	FASEB journal : official publication of the Federation of American Societies for Experimental Biology	2012	PMID: 22835832
Screening of mutations in genes that predispose to hereditary paragangliomas and pheochromocytomas.	Lefebvre S	Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme	2012	PMID: 22517554
Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management.	Hermsen MA	Cellular oncology : the official journal of the International Society for Cellular Oncology	2010	PMID: 20208144
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
Chromosomal changes in sporadic and familial head and neck paragangliomas.	Sevilla MA	Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery	2009	PMID: 19393419
Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.	Neumann HP	Cancer research	2009	PMID: 19351833
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
A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.	Dahia PL	PLoS genetics	2005	PMID: 16103922
Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.	Gimenez-Roqueplo AP	Cancer research	2003	PMID: 14500403
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Text-mined citations for rs138996609 ...

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Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_003000.3(SDHB):c.688C>T (p.Arg230Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs138996609 ...