NM_003001.5(SDHC):c.148C>T (p.Arg50Cys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Aug 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000492504.4

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]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000581221Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Aug 6, 2020)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, et al.

Cancer Res. 2009 Apr 15;69(8):3650-6. doi: 10.1158/0008-5472.CAN-08-4057. Epub 2009 Apr 7.

PubMed [citation]
PMID:
19351833

Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome.

Panizza E, Ercolino T, Mori L, Rapizzi E, Castellano M, Opocher G, Ferrero I, Neumann HP, Mannelli M, Goffrini P.

Hum Mol Genet. 2013 Feb 15;22(4):804-15. doi: 10.1093/hmg/dds487. Epub 2012 Nov 21.

PubMed [citation]
PMID:
23175444
See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000581221.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (10)

Description

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 position 148. The arginine at codon 50 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been detected in multiple individuals with personal or family history of pheochromocytoma and/or paraganglioma (Neumann HP et al. Cancer Res. 2009 Apr 15;69:3650-6; Rattenberry E et al. J. Clin. Endocrinol. Metab. 2013 Jul;98:E1248-56; McInerney-Leo AM et al. Clin. Endocrinol. (Oxf) 2014 Jan;80:25-33; Bennedbaek M et al. Hered. Cancer Clin. Pract. 2016 Jun;14:13; Andrews KA et al. J. Med. Genet., 2018 Jun;55:384-394; Casey RT et al. Sci Rep, 2019 07;9:10244). In a yeast-based functional study, this alteration resulted in a significant reduction of SDH enzyme activity (Panizza E et al. Hum. Mol. Genet. 2013 Feb;22:804-15). 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 majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jul 7, 2021

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