VCV000187084.21 - ClinVar

NM_003001.5(SDHC):c.380A>G (p.His127Arg)

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_003001.5(SDHC):c.380A>G (p.His127Arg)

Variation ID: 187084 Accession: VCV000187084.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q23.3 1: 161356815 (GRCh38) [ NCBI UCSC ] 1: 161326605 (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	Dec 19, 2017	Jun 17, 2024	Feb 8, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003001.5:c.380A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002992.1:p.His127Arg	missense
NM_001035511.3:c.242-5514A>G		intron variant
NM_001035512.3:c.278A>G	NP_001030589.1:p.His93Arg	missense
NM_001035513.3:c.221A>G	NP_001030590.1:p.His74Arg	missense
NM_001278172.3:c.140-5514A>G		intron variant
NM_001407115.1:c.500A>G	NP_001394044.1:p.His167Arg	missense
NM_001407116.1:c.323A>G	NP_001394045.1:p.His108Arg	missense
NM_001407117.1:c.317A>G	NP_001394046.1:p.His106Arg	missense
NM_001407118.1:c.272A>G	NP_001394047.1:p.His91Arg	missense
NM_001407119.1:c.269A>G	NP_001394048.1:p.His90Arg	missense
NM_001407120.1:c.269A>G	NP_001394049.1:p.His90Arg	missense
NM_001407121.1:c.185-5514A>G		intron variant
NR_103459.3:n.432A>G		non-coding transcript variant
NC_000001.11:g.161356815A>G
NC_000001.10:g.161326605A>G
NG_012767.1:g.47440A>G
LRG_317:g.47440A>G
LRG_317t1:c.380A>G	LRG_317p1:p.His127Arg

... more HGVS ... less HGVS

Protein change

H127R, H74R, H93R, H106R, H167R, H91R, H108R, H90R

Other names

Canonical SPDI

NC_000001.11:161356814:A:G

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.

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

Trans-Omics for Precision Medicine (TOPMed) 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Links

ClinGen: CA011435 dbSNP: rs786203457 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.
SDHC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	862	904

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	May 27, 2021	RCV000166772.10
not provided	Likely pathogenic (1)	criteria provided, single submitter	Dec 3, 2022	RCV000478217.7
Gastrointestinal stromal tumor Paragangliomas 3	Pathogenic (1)	criteria provided, single submitter	Jan 16, 2024	RCV000641906.9
Gastrointestinal stromal tumor	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Dec 7, 2023	RCV001523820.5
Hereditary pheochromocytoma-paraganglioma	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 2, 2023	RCV003995530.2
Paragangliomas 3	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Feb 8, 2024	RCV004019988.2

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.
Likely pathogenic (Dec 15, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Gastrointestinal stromal tumor Affected status: no Allele origin: germline	Department of Pediatrics, Memorial Sloan Kettering Cancer Center Accession: SCV001478182.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Publications: PubMed (1) PubMed: 28873162
Likely pathogenic (Dec 03, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000565547.5 First in ClinVar: Apr 27, 2017 Last updated: Dec 31, 2022	Comment: In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); … (more) In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23162105, 29386252, 25025441, 31579262, 19332149, 23666964, 26259135, 25494863, 23282968, 25394176, 24886695, 26273102, 23833252, 24625421, 24096523, 27011036, 33087929, 34703596, 34558728, 33237286, 24150194, 34308366, 34110302, 34301805) (less)
Pathogenic (Jan 16, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Paragangliomas 3 Gastrointestinal stromal tumor 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: SCV000763556.6 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024	Publications: PubMed (6) PubMed: 28492532‚ 23666964‚ 24150194‚ 25494863‚ 22517557‚ 24758179 Comment: This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 127 of the SDHC protein (p.His127Arg). … (more) This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 127 of the SDHC protein (p.His127Arg). This variant is present in population databases (rs786203457, gnomAD no frequency). This missense change has been observed in individuals with gastrointestinal stromal tumor, renal carcinoma and papillary thyroid carcinoma and paraganglioma (PMID: 23666964, 24150194, 25494863; Invitae). ClinVar contains an entry for this variant (Variation ID: 187084). 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 SDHC protein function with a positive predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). This variant disrupts the p.His127 amino acid residue in SDHC. Other variant(s) that disrupt this residue have been observed in individuals with SDHC-related conditions (PMID: 22517557, 24758179), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. (less)
Likely Pathogenic (Oct 02, 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: SCV004836972.1 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 (12) PubMed: 15989954‚ 19332149‚ 23282968‚ 23666964‚ 24150194‚ 24625421‚ 25025441‚ 25494863‚ 29386252‚ 31308404‚ 34110302‚ 34558728 Comment: This missense variant replaces histidine with arginine at codon 127 of the SDHC protein. Computational prediction suggests that this variant may have deleterious impact on … (more) This missense variant replaces histidine with arginine at codon 127 of the SDHC 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). To our knowledge, functional studies have not been reported for this variant, however histidine-127 is a key amino acid for heme binding (PMID: 15989954) and mutations of this residue abolish SDHC protein levels, destabilize of SDHD and SDHB level, and abrogate both succinate ubiquinone oxidoreductase (SQR) and succinate dehydrogenase (SDH) (complex II) enzymatic activities in mitochondria (PMID: 19332149). This variant has been reported in individuals affected with paragangliomas, gastrointestinal stromal tumors (GIST), renal cell carcinoma, and pituitary adenomas (PMID: 23282968, 23666964, 24150194, 24625421, 25025441, 25494863, 29386252, 31308404, 34110302, 34558728). This variant has been identified in 1/31390 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less) Number of individuals with the variant: 1
Likely Pathogenic (Aug 10, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary pheochromocytoma-paraganglioma (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847997.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Publications: PubMed (5) PubMed: 24150194‚ 23282968‚ 31308404‚ 23666964‚ 25494863 Comment: The p.His127Arg variant in SDHC has been reported in 6 individuals with SDHC-related tumors and segregated with disease in 1 affected individual from 1 family … (more) The p.His127Arg variant in SDHC has been reported in 6 individuals with SDHC-related tumors and segregated with disease in 1 affected individual from 1 family (Gill 2013 PMID: 24150194; Miettinen 2013 PMID: 23282968; Denes 2015 PMID: 25494863; Rattenberry 2013 PMID: 23666964; Casey 2019 PMID 31308404; Invitae). It was absent from large population studies. This variant has also been reported in ClinVar (Variation ID 187084). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant SDHC-related tumors. ACMG/AMP Criteria applied: PM2, PP3, PS4_Strong. (less)
Likely pathogenic (Feb 08, 2024)	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) Method: clinical testing	Paragangliomas 3 Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV004933699.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 25494863‚ 24150194‚ 23666964 Comment: This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 25494863, 24150194, 23666964]. This … (more) This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 25494863, 24150194, 23666964]. This variant is expected to disrupt protein structure [Myriad internal data]. (less)
Pathogenic (May 27, 2021)	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: SCV000217585.8 First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024	Publications: PubMed (15) PubMed: 15989954‚ 18491383‚ 19332149‚ 22517557‚ 23162105‚ 23282968‚ 23666964‚ 24096523‚ 24150194‚ 24625421‚ 25025441‚ 25394176‚ 25494863‚ 29386252‚ 31308404 Comment: The p.H127R pathogenic mutation (also known as c.380A>G), located in coding exon 5 of the SDHC gene, results from an A to G substitution at … (more) The p.H127R pathogenic mutation (also known as c.380A>G), located in coding exon 5 of the SDHC gene, results from an A to G substitution at nucleotide position 380. The histidine at codon 127 is replaced by arginine, an amino acid with highly similar properties. The mutation has been detected in multiple individuals with paraganglioma(s) (Rattenberry E et al. J Clin Endocrinol Metab, 2013 Jul;98:E1248-56; Dénes J et al. J Clin Endocrinol Metab, 2015 Mar;100:E531-41; Andrews KA et al. J Med Genet, 2018 06;55:384-394; Ambry internal data). It has also been identified in patients with a succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor and/or renal carcinoma (Gill AJ et al. Pathology, 2013 12;45:689-91; Gill AJ et al. Am J Surg Pathol, 2014 Dec;38:1588-602; Casey RT et al. Sci Rep, 2019 07;9:10244; Ambry internal data). Based on internal structural analysis, this mutation disrupts the SDHC heme-binding site, within which there are other internally pathogenic variants (Sun F et al. Cell, 2005 Jul;121:1043-57; Fufezan C et al. Proteins, 2008 Nov;73:690-704; Lemarie A et al. Mitochondrion, 2009 Jul;9:254-60). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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)
Likely pathogenic (Dec 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	paragangliomas 3 Affected status: unknown Allele origin: unknown	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine Accession: SCV005045796.1 First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024
Pathogenic (Dec 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Gastrointestinal stromal tumor Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004203056.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024

Comment:

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23162105, 29386252, 25025441, 31579262, 19332149, 23666964, 26259135, 25494863, 23282968, 25394176, 24886695, 26273102, 23833252, 24625421, 24096523, 27011036, 33087929, 34703596, 34558728, 33237286, 24150194, 34308366, 34110302, 34301805)

Comment:

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 127 of the SDHC protein (p.His127Arg). This variant is present in population databases (rs786203457, gnomAD no frequency). This missense change has been observed in individuals with gastrointestinal stromal tumor, renal carcinoma and papillary thyroid carcinoma and paraganglioma (PMID: 23666964, 24150194, 25494863; Invitae). ClinVar contains an entry for this variant (Variation ID: 187084). 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 SDHC protein function with a positive predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). This variant disrupts the p.His127 amino acid residue in SDHC. Other variant(s) that disrupt this residue have been observed in individuals with SDHC-related conditions (PMID: 22517557, 24758179), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

Comment:

This missense variant replaces histidine with arginine at codon 127 of the SDHC 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). To our knowledge, functional studies have not been reported for this variant, however histidine-127 is a key amino acid for heme binding (PMID: 15989954) and mutations of this residue abolish SDHC protein levels, destabilize of SDHD and SDHB level, and abrogate both succinate ubiquinone oxidoreductase (SQR) and succinate dehydrogenase (SDH) (complex II) enzymatic activities in mitochondria (PMID: 19332149). This variant has been reported in individuals affected with paragangliomas, gastrointestinal stromal tumors (GIST), renal cell carcinoma, and pituitary adenomas (PMID: 23282968, 23666964, 24150194, 24625421, 25025441, 25494863, 29386252, 31308404, 34110302, 34558728). This variant has been identified in 1/31390 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

Comment:

The p.His127Arg variant in SDHC has been reported in 6 individuals with SDHC-related tumors and segregated with disease in 1 affected individual from 1 family (Gill 2013 PMID: 24150194; Miettinen 2013 PMID: 23282968; Denes 2015 PMID: 25494863; Rattenberry 2013 PMID: 23666964; Casey 2019 PMID 31308404; Invitae). It was absent from large population studies. This variant has also been reported in ClinVar (Variation ID 187084). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant SDHC-related tumors. ACMG/AMP Criteria applied: PM2, PP3, PS4_Strong.

Comment:

This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 25494863, 24150194, 23666964]. This variant is expected to disrupt protein structure [Myriad internal data].

Comment:

The p.H127R pathogenic mutation (also known as c.380A>G), located in coding exon 5 of the SDHC gene, results from an A to G substitution at nucleotide position 380. The histidine at codon 127 is replaced by arginine, an amino acid with highly similar properties. The mutation has been detected in multiple individuals with paraganglioma(s) (Rattenberry E et al. J Clin Endocrinol Metab, 2013 Jul;98:E1248-56; Dénes J et al. J Clin Endocrinol Metab, 2015 Mar;100:E531-41; Andrews KA et al. J Med Genet, 2018 06;55:384-394; Ambry internal data). It has also been identified in patients with a succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor and/or renal carcinoma (Gill AJ et al. Pathology, 2013 12;45:689-91; Gill AJ et al. Am J Surg Pathol, 2014 Dec;38:1588-602; Casey RT et al. Sci Rep, 2019 07;9:10244; Ambry internal data). Based on internal structural analysis, this mutation disrupts the SDHC heme-binding site, within which there are other internally pathogenic variants (Sun F et al. Cell, 2005 Jul;121:1043-57; Fufezan C et al. Proteins, 2008 Nov;73:690-704; Lemarie A et al. Mitochondrion, 2009 Jul;9:254-60). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

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
SDHC phaeochromocytoma and paraganglioma: A UK-wide case series.	Williams ST	Clinical endocrinology	2022	PMID: 34558728
Cabergoline reduces 3-methoxytyramine in a SDHC patient with metastatic paraganglioma and prolactinoma.	Hussein Z	Endocrinology, diabetes & metabolism case reports	2021	PMID: 34110302
SDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice.	Casey RT	Scientific reports	2019	PMID: 31308404
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
Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.	Mandelker D	JAMA	2017	PMID: 28873162
Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.	Dénes J	The Journal of clinical endocrinology and metabolism	2015	PMID: 25494863
Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations.	Evenepoel L	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25394176
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
The clinical phenotype of SDHC-associated hereditary paraganglioma syndrome (PGL3).	Else T	The Journal of clinical endocrinology and metabolism	2014	PMID: 24758179
Succinate dehydrogenase deficiency is rare in pituitary adenomas.	Gill AJ	The American journal of surgical pathology	2014	PMID: 24625421
Germline SDHC mutation presenting as recurrent SDH deficient GIST and renal carcinoma.	Gill AJ	Pathology	2013	PMID: 24150194
Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis.	Papathomas TG	European journal of endocrinology	2013	PMID: 24096523
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
Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation.	Miettinen M	The American journal of surgical pathology	2013	PMID: 23282968
Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators.	Gimenez-Roqueplo AP	The Journal of clinical endocrinology and metabolism	2013	PMID: 23162105
A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma.	Buffet A	Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme	2012	PMID: 22517557
Mutations in the heme b-binding residue of SDHC inhibit assembly of respiratory chain complex II in mammalian cells.	Lemarie A	Mitochondrion	2009	PMID: 19332149
Ligand preference and orientation in b- and c-type heme-binding proteins.	Fufezan C	Proteins	2008	PMID: 18491383
Crystal structure of mitochondrial respiratory membrane protein complex II.	Sun F	Cell	2005	PMID: 15989954
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Text-mined citations for rs786203457 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_003001.5(SDHC):c.380A>G (p.His127Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs786203457 ...