ClinVar Genomic variation as it relates to human health
NM_003000.3(SDHB):c.725G>A (p.Arg242His)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003000.3(SDHB):c.725G>A (p.Arg242His)
Variation ID: 12781 Accession: VCV000012781.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.13 1: 17022648 (GRCh38) [ NCBI UCSC ] 1: 17349143 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Sep 4, 2016 Mar 10, 2024 Jan 21, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003000.3:c.725G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002991.2:p.Arg242His missense NC_000001.11:g.17022648C>T NC_000001.10:g.17349143C>T NG_012340.1:g.36523G>A LRG_316:g.36523G>A LRG_316t1:c.725G>A LRG_316p1:p.Arg242His P21912:p.Arg242His - Protein change
- R242H
- Other names
- p.R242H:CGC>CAC
- Canonical SPDI
- NC_000001.11:17022647:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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 | ||
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HI score
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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. |
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SDHB | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
1253 | 1370 |
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. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 5, 2021 | RCV000013619.35 | |
Pathogenic (2) |
criteria provided, single submitter
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Aug 20, 2021 | RCV000022778.29 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 8, 2022 | RCV000129095.10 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Aug 2, 2023 | RCV000183216.21 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 27, 2023 | RCV000505354.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 21, 2024 | RCV000627751.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 14, 2022 | RCV001836632.4 |
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. |
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Pathogenic
(Jan 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000235636.16
First in ClinVar: Jul 05, 2015 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect: significantly reduced SDH/complex II activity and abrogated SDHAF3 interaction (Kim et al., 2015; Nesti et al., 2015; Dwight … (more)
Published functional studies demonstrate a damaging effect: significantly reduced SDH/complex II activity and abrogated SDHAF3 interaction (Kim et al., 2015; Nesti et al., 2015; Dwight et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12213855, 19393419, 23433498, 25025441, 17102084, 29925701, 34906457, 32782288, 24606901, 22835832, 25736212, 12000816, 25972245, 21173220, 20208144, 22293219, 19258401, 17652212, 19802898, 22270996, 25047027, 19454582, 18551016, 28374168, 25899001, 27573198, 15328326, 24276837, 25873086, 19075037, 16317055, 28503760, 29386252, 29204718, 29951630, 29800631, 29950348, 28748451, 31212687, 30549360, 31104306, 30658386, 28490599, 31492822, 30050099, 26464466, 31589614, 32741965, 33644666, 30787465, 28738844) (less)
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Pathogenic
(Nov 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000183806.9
First in ClinVar: Aug 06, 2014 Last updated: Apr 15, 2023 |
Comment:
The p.R242H pathogenic mutation (also known as c.725G>A), located in coding exon 7 of the SDHB gene, results from a G to A substitution at … (more)
The p.R242H pathogenic mutation (also known as c.725G>A), located in coding exon 7 of the SDHB gene, results from a G to A substitution at nucleotide position 725. The arginine at codon 242 is replaced by histidine, an amino acid with highly similar properties. The p.R242H mutation has been well described in published literature. It has been identified in numerous individuals with tumors across the paraganglioma-pheochromocytoma (PGL-PCC) syndrome spectrum, including thoracic, pelvic, and head and neck PGL, adrenal PCC, and renal cell carcinoma (Neumann HP et al. JAMA. 2004 Aug;292:943-51; Ghayee HK et al. Endocr. Relat. Cancer. 2009 Mar;16:291-9; Luiz HV et al. Pediatrics. 2013 Dec;32:e1709-14; Persu A et al. J. Hypertens. 2008 Jul;26:1395-401; Burnichon N et al. J. Clin. Endocrinol. Metab. 2009 Aug;94:2817-27; Merlo A et al. J. Clin. Endocrinol. Metab 2013 Oct;98:E1661-6; Rattenberry E et al. J. Clin. Endocrinol. Metab. 2013 Jul;98:E1248-56; van Hulsteijn LT et al. Fam. Cancer. 2014 Dec;13:651-7; Janssen I et al. Clin. Cancer Res. 2015 Sep;21:3888-95; Gill AJ et al. Am. J. Surg. Pathol. 2014 Dec;38:1588-602). In one study, mutant yeast strains with this mutation showed a significant defect and structural analysis suggested that this mutation alters the conformation of the protein, causing a decrease in the positive surface extent of the mutant protein (Nesti C et al. Hum. Mol. Genet. 2015 Jun;24:3248-56). Additionally, structural modeling of this mutation has predicted disruption of the electron path and impaired functional activity (Kim E et al. Endocr. Relat. Cancer. 2015 Jun;22:387-97). Of note, two different alterations at the same codon, p.R242C and p.R242S, have also been reported in patients with head/neck PGLs and PCCs (Panizza E et al. Hum. Mol. Genet. 2013 Feb;22:804-15; Neumann HP et al. Cancer Res. 2009 Apr;69:3650-6; Lefebvre S et al. Horm. Metab. Res. 2012 May;44:334-8; Badenhop RF et al. J. Med. Genet. 2004 Jul;41:e99). Based on the available evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Apr 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pheochromocytoma-paraganglioma
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003929309.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
Variant summary: SDHB c.725G>A (p.Arg242His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: SDHB c.725G>A (p.Arg242His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251440 control chromosomes. c.725G>A has been reported in the literature in multiple individuals affected with features of Hereditary Paraganglioma-Pheochromocytoma Syndrome (example, Persu_2008, Amar_2007, Young_2002, Benn_2006, Neumann_2004, Neumann_2002). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 12000816, 17652212, 16317055, 15328326, 18551016, 12213855). Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001746833.11
First in ClinVar: Jul 10, 2021 Last updated: Mar 10, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Apr 17, 2019)
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criteria provided, single submitter
Method: clinical testing
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Paragangliomas 4
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367997.2
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.
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Pathogenic
(Feb 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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SDHB-Related Disorders
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002097298.1
First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022 |
Comment:
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 25972245; 25736212; 22835832) - PS3. … (more)
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 25972245; 25736212; 22835832) - PS3. The c.725G>A;p.(Arg242His) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 12781; OMIM: 185470.0004; PMID: 12000816; 20208144; 24276837; 12213855; 17102084; 22270996) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Fer4) - PM1. This variant is not present in population databases (rs7431536, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 239443 - c.724C>A (p.Arg242Ser); ClinVar ID: 186827 - c.724C>T (p.Arg242Cys)) - PM5. Missense variant in SDHB that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Jul 06, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002527089.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Pathogenic
(Oct 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Paragangliomas 4
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580428.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Nov 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pheochromocytoma-paraganglioma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761484.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The SDHB c.725G>A variant is a single nucleotide substitution from a guanine to an adenonine at position 725 which is predicted to change the arginine … (more)
The SDHB c.725G>A variant is a single nucleotide substitution from a guanine to an adenonine at position 725 which is predicted to change the arginine at position 242 in the protein to histidine. The variant has been reported multiple times in the literature in association with disease (PMID: 12000816, 12213855, 15328326, 28490599) (PS1). Functional studies demonstrate that the variant has a detrimental effect on protein function (PMID: 25972245, 22835832) (PS3). The variant is listed in dbSNP (rs74315368) and is rare in population databases (gnomAD 3 het/251,440 total, 0 hom). The variant is described in ClinVar as pathogenic (ClinVar ID: 27820) and HGMD (2020.3) as disease causing (PP5). Computational predictions support a deleterious effect on the gene or gene product. (less)
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Likely pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010041.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Aug 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Gastrointestinal stromal tumor
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004203045.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 12, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220335.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000012 (3/251440 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been … (more)
The frequency of this variant in the general population, 0.000012 (3/251440 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in multiple individuals affected with PGL-PCC syndrome (PMID: 12000816 (2002), 12213855 (2002), 18551016 (2008), 19351833 (2009), 29386252 (2018), 34439168 (2021), 34906457 (2022)). Functional studies observed decreased stability of the SDHB protein (PMID: 22835832 (2012)) and a severe decrease in succinate dehydrogenase activity (PMID: 25736212 (2015), 25972245 (2015)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Aug 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004563897.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The SDHB c.725G>A; p.Arg242His variant (rs74315368) is reported in the literature in individuals affected with paraganglioma or pheochromocytoma (Luiz 2013, Neumann 2002, Neumann 2009, Niemeijer … (more)
The SDHB c.725G>A; p.Arg242His variant (rs74315368) is reported in the literature in individuals affected with paraganglioma or pheochromocytoma (Luiz 2013, Neumann 2002, Neumann 2009, Niemeijer 2017, Young 2002). In at least one family, this variant was observed to segregate with disease (Young 2002). This variant is also reported in ClinVar (Variation ID: 12781). It is only found on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.944). Consistent with these predictions, functional assays have observed that this variant exhibits decreased SDH/complex II activity (Kim 2015, Nesti 2015) and increased ubiquitination (Yang 2012). Additionally, other amino acid substitutions at this codon (p.Arg242Cys, p.Arg242Ser) have been reported in individuals with paraganglioma and are considered pathogenic (Badenhop 2004, Neumann 2009). Based on available information, the p.Arg242His variant is considered to be pathogenic. References: Badenhop RF et al. The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features. J Med Genet. 2004 Jul;41(7):e99. PMID: 15235042. Kim E et al. Structural and functional consequences of succinate dehydrogenase subunit B mutations. Endocr Relat Cancer. 2015 Jun;22(3):387-97. PMID: 25972245. Luiz HV et al. Malignant paraganglioma presenting with hemorrhagic stroke in a child. Pediatrics. 2013 Dec;132(6):e1709-14. PMID: 24276837. Nesti C et al. Additive effect of nuclear and mitochondrial mutations in a patient with mitochondrial encephalomyopathy. Hum Mol Genet. 2015 Jun 1;24(11):3248-56. PMID: 25736212. Neumann HP et al. Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out. Cancer Res. 2009 Apr 15;69(8):3650-6. PMID: 19351833. Neumann HP et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002 May 9;346(19):1459-66. PMID: 12000816. Niemeijer ND et al. The phenotype of SDHB germline mutation carriers: a nationwide study. Eur J Endocrinol. 2017 Aug;177(2):115-125. PMID: 28490599. Yang C et al. Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function. FASEB J. 2012 Nov;26(11):4506-16. PMID: 22835832. Young AL et al. Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. J Clin Endocrinol Metab. 2002 Sep;87(9):4101-5. PMID: 12213855. (less)
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Pathogenic
(Jan 21, 2024)
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criteria provided, single submitter
Method: clinical testing
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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
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Invitae
Accession: SCV000644767.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 242 of the SDHB protein (p.Arg242His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 242 of the SDHB protein (p.Arg242His). This variant is present in population databases (rs74315368, gnomAD 0.007%). This missense change has been observed in individuals with sporadic and familial hereditary paragangliomas and/or pheochromocytomas (PMID: 12000816, 12213855, 17102084, 20208144, 21173220, 22270996, 24276837, 25736212). ClinVar contains an entry for this variant (Variation ID: 12781). 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, 25736212, 25972245). This variant disrupts the p.Arg242 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (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)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Hereditary pheochromocytoma-paraganglioma
Affected status: yes
Allele origin:
germline
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Section on Medical Neuroendocrinolgy, National Institutes of Health
Accession: SCV000599525.1
First in ClinVar: Sep 15, 2017 Last updated: Sep 15, 2017 |
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Pathogenic
(Oct 17, 2023)
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no assertion criteria provided
Method: literature only
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PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 4
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000033866.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 21, 2023 |
Comment on evidence:
In a man and his son, both of whom had metastatic catecholamine-secreting paragangliomas (PPGL4; 115310), Young et al. (2002) identified a 725G-A transition in exon … (more)
In a man and his son, both of whom had metastatic catecholamine-secreting paragangliomas (PPGL4; 115310), Young et al. (2002) identified a 725G-A transition in exon 7 of the SDHB gene, resulting in an arg242-to-his (R242H) substitution. Sequencing of the SDHB gene in the tumors did not reveal any somatic mutations or loss of heterozygosity of the remaining allele. Neumann et al. (2002) identified the R242H substitution in the germline of a patient with sporadic pheochromocytoma. The mutation was not identified in 600 control chromosomes. Janeway et al. (2011) identified a germline R242H mutation in a 21-year-old patient with a sporadic gastrointestinal stromal tumor (GIST; 606764). (less)
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Pathogenic
(Jan 04, 2011)
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no assertion criteria provided
Method: literature only
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GASTROINTESTINAL STROMAL TUMOR
Affected status: not provided
Allele origin:
unknown
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OMIM
Accession: SCV000044067.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 21, 2023 |
Comment on evidence:
In a man and his son, both of whom had metastatic catecholamine-secreting paragangliomas (PPGL4; 115310), Young et al. (2002) identified a 725G-A transition in exon … (more)
In a man and his son, both of whom had metastatic catecholamine-secreting paragangliomas (PPGL4; 115310), Young et al. (2002) identified a 725G-A transition in exon 7 of the SDHB gene, resulting in an arg242-to-his (R242H) substitution. Sequencing of the SDHB gene in the tumors did not reveal any somatic mutations or loss of heterozygosity of the remaining allele. Neumann et al. (2002) identified the R242H substitution in the germline of a patient with sporadic pheochromocytoma. The mutation was not identified in 600 control chromosomes. Janeway et al. (2011) identified a germline R242H mutation in a 21-year-old patient with a sporadic gastrointestinal stromal tumor (GIST; 606764). (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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An exploration in pitfalls in interpreting SDHB immunohistochemistry. | Ding CC | Histopathology | 2022 | PMID: 35546442 |
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 |
Genetic spectrum in a Canadian cohort of apparently sporadic pheochromocytomas and paragangliomas: New data on multigene panel retesting over time. | Parisien-La Salle S | Clinical endocrinology | 2022 | PMID: 34750850 |
Prevalence of Germline Variants in a Large Cohort of Japanese Patients with Pheochromocytoma and/or Paraganglioma. | Yonamine M | Cancers | 2021 | PMID: 34439168 |
Mutation Profile of Aggressive Pheochromocytoma and Paraganglioma with Comparison of TCGA Data. | Choi YM | Cancers | 2021 | PMID: 34069252 |
Identification of a novel SDHB c.563 T > C mutation responsible for Paraganglioma syndrome and genetic analysis of the SDHB gene in China: a case report. | Chen H | BMC medical genetics | 2020 | PMID: 32460727 |
Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations. | Rijken JA | BJS open | 2018 | PMID: 29951630 |
A Novel SDHB IVS2-2A>C Mutation Is Responsible for Hereditary Pheochromocytoma/Paraganglioma Syndrome. | Yamanaka M | The Tohoku journal of experimental medicine | 2018 | PMID: 29925701 |
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 |
The phenotype of SDHB germline mutation carriers: a nationwide study. | Niemeijer ND | European journal of endocrinology | 2017 | PMID: 28490599 |
Structural and functional consequences of succinate dehydrogenase subunit B mutations. | Kim E | Endocrine-related cancer | 2015 | PMID: 25972245 |
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 |
Additive effect of nuclear and mitochondrial mutations in a patient with mitochondrial encephalomyopathy. | Nesti C | Human molecular genetics | 2015 | PMID: 25736212 |
SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). | Papathomas TG | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 2015 | PMID: 25720320 |
Phenotype of SDHB mutation carriers in the Netherlands. | van Hulsteijn LT | Familial cancer | 2014 | PMID: 25047027 |
Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. | Gill AJ | The American journal of surgical pathology | 2014 | PMID: 25025441 |
Malignant paraganglioma presenting with hemorrhagic stroke in a child. | Luiz HV | Pediatrics | 2013 | PMID: 24276837 |
Identification of somatic VHL gene mutations in sporadic head and neck paragangliomas in association with activation of the HIF-1α/miR-210 signaling pathway. | Merlo A | The Journal of clinical endocrinology and metabolism | 2013 | PMID: 23902947 |
A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma. | Rattenberry E | The Journal of clinical endocrinology and metabolism | 2013 | PMID: 23666964 |
Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome. | Panizza E | Human molecular genetics | 2013 | PMID: 23175444 |
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 |
Identification of three new variants of SDHx genes in a cohort of Portuguese patients with extra-adrenal paragangliomas. | Domingues R | Journal of endocrinological investigation | 2012 | PMID: 22293219 |
Prevalence of germline mutations in patients with pheochromocytoma or abdominal paraganglioma and sporadic presentation: a population-based study in Western Sweden. | Muth A | World journal of surgery | 2012 | PMID: 22270996 |
Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. | Janeway KA | Proceedings of the National Academy of Sciences of the United States of America | 2011 | PMID: 21173220 |
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 |
Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior. | Ghayee HK | Endocrine-related cancer | 2009 | PMID: 19075037 |
High prevalence of SDHB mutations in head and neck paraganglioma in Belgium. | Persu A | Journal of hypertension | 2008 | PMID: 18551016 |
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 |
Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. | Neumann HP | JAMA | 2004 | PMID: 15328326 |
The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features. | Badenhop RF | Journal of medical genetics | 2004 | PMID: 15235042 |
Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. | Young AL | The Journal of clinical endocrinology and metabolism | 2002 | PMID: 12213855 |
Germ-line mutations in nonsyndromic pheochromocytoma. | Neumann HP | The New England journal of medicine | 2002 | PMID: 12000816 |
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HelpRecord last updated Mar 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.