NM_003001.5(SDHC):c.148C>T (p.Arg50Cys) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jul 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000756631.1

Allele description [Variation Report for NM_003001.5(SDHC):c.148C>T (p.Arg50Cys)]

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

Gene:
SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.3
Genomic location:
Preferred name:
NM_003001.5(SDHC):c.148C>T (p.Arg50Cys)
HGVS:
  • NC_000001.11:g.161328466C>T
  • NG_012767.1:g.19091C>T
  • NM_001035511.2:c.148C>T
  • NM_001035512.2:c.77+4796C>T
  • NM_001035513.2:c.21-12128C>T
  • NM_001278172.2:c.77+4796C>T
  • NM_003001.3:c.148C>T
  • NM_003001.5:c.148C>TMANE SELECT
  • NP_001030588.1:p.Arg50Cys
  • NP_002992.1:p.Arg50Cys
  • NP_002992.1:p.Arg50Cys
  • LRG_317t1:c.148C>T
  • LRG_317:g.19091C>T
  • LRG_317p1:p.Arg50Cys
  • NC_000001.10:g.161298256C>T
  • NR_103459.1:n.178C>T
  • NR_103459.2:n.173C>T
  • p.Arg50Cys
Protein change:
R50C
Links:
dbSNP: rs587778661
NCBI 1000 Genomes Browser:
rs587778661
Molecular consequence:
  • NM_001035512.2:c.77+4796C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001035513.2:c.21-12128C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001278172.2:c.77+4796C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001035511.2:c.148C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003001.3:c.148C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003001.5:c.148C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_103459.2:n.173C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000884502ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Jul 5, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000884502.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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, the variant has also been described in a healthy population (Bodian 2014). The variant is listed in the ClinVar database (Variation ID: 135194) and the dbSNP variant database (rs587778661) but is not described in the general population-based databases (Exome Variant Server, Genome Aggregation Database). The amino acid at this position is highly conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is deleterious. In agreement with the predictions, at least one functional study in yeast describes a mild effect on activity (Panizza 2013). However, based on available information, there is insufficient evidence to classify the variant with certainty. References: Bennedbaek M et al. Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients. Hered Cancer Clin Pract. 2016 Jun 8;14:13. Bodian DL et al. Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. PLoS One. 2014 Apr 11;9(4):e94554. 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. Panizza E et al. Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome. Hum Mol Genet. 2013 Feb 15;22(4):804-15. Rattenberry E et al. A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2013 Jul;98(7):E1248-56.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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