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NM_003001.5(SDHC):c.148C>T (p.Arg50Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 8, 2020
Accession:
VCV000135194.7
Variation ID:
135194
Description:
single nucleotide variant
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NM_003001.5(SDHC):c.148C>T (p.Arg50Cys)

Allele ID
138933
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q23.3
Genomic location
1: 161328466 (GRCh38) GRCh38 UCSC
1: 161298256 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.11:g.161328466C>T
NC_000001.10:g.161298256C>T
NM_003001.5:c.148C>T MANE Select NP_002992.1:p.Arg50Cys missense
... more HGVS
Protein change
R50C
Other names
-
Canonical SPDI
NC_000001.11:161328465:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
ClinGen: CA011515
dbSNP: rs587778661
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Aug 6, 2020 RCV000492504.4
Likely pathogenic 1 criteria provided, single submitter Aug 8, 2020 RCV000641913.5
Uncertain significance 1 criteria provided, single submitter Jul 5, 2017 RCV000756631.1
Likely pathogenic 1 criteria provided, single submitter Feb 9, 2018 RCV000826184.1
not provided 1 no assertion provided Sep 19, 2013 RCV000122003.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SDHC Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
493 522

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jul 05, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000884502.1
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The SDHC c.148C>T;p.Arg50Cys variant has been described in the medical literature in individuals with head and neck paraganglioma (Bennedbaek 2016, Neumann 2009, Rattenberry 2013). However, … (more)
Likely pathogenic
(Feb 09, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary Paraganglioma-Pheochromocytoma Syndromes
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000967727.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (7)
Comment:
The p.Arg50Cys variant in SDHC has been reported in 4 individuals with hereditar y paraganglioma-pheochromocytoma syndrome (Neuman 2009, Rattenberry 2013, McIner ney-Leo 2014, Bennedbaek 2016), … (more)
Likely pathogenic
(Aug 06, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000581221.4
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (10)
Comment:
The p.R50C variant (also known as c.148C>T), located in coding exon 3 of the SDHC gene, results from a C to T substitution at nucleotide … (more)
Likely pathogenic
(Aug 08, 2020)
criteria provided, single submitter
Method: clinical testing
Paragangliomas 3
Gastrointestinal stromal tumor
Allele origin: germline
Invitae
Accession: SCV000763563.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces arginine with cysteine at codon 50 of the SDHC protein (p.Arg50Cys). The arginine residue is highly conserved and there is a … (more)
not provided
(Sep 19, 2013)
no assertion provided
Method: reference population
AllHighlyPenetrant
Allele origin: germline
ITMI
Accession: SCV000086214.1
Submitted: (May 29, 2014)
Comment:
Please see associated publication for description of ethnicities
Evidence details
Publications
PubMed (1)

Functional evidence

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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 this variant

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Title Author Journal Year Link
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 <i>SDHB</i>, <i>SDHC</i> and <i>SDHD</i>. Andrews KA Journal of medical genetics 2018 PMID: 29386252
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients. Bennedbæk M Hereditary cancer in clinical practice 2016 PMID: 27279923
15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1-5. Benn DE Endocrine-related cancer 2015 PMID: 26273102
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
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. Bodian DL PloS one 2014 PMID: 24728327
Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas. McInerney-Leo AM Clinical endocrinology 2014 PMID: 24102379
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
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

Text-mined citations for rs587778661...

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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 Jul 07, 2021