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

Clinical significance:Likely pathogenic (Last evaluated: Aug 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000641913.5

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)

Name:
Gastrointestinal stromal tumor (GIST)
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 3 (PGL3)
Synonyms:
Glomus tumors, familial, 3; SDHC-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 3)
Identifiers:
MONDO: MONDO:0011544; MedGen: C1854336; Orphanet: 29072; OMIM: 605373

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000763563Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 8, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas.

McInerney-Leo AM, Marshall MS, Gardiner B, Benn DE, McFarlane J, Robinson BG, Brown MA, Leo PJ, Clifton-Bligh RJ, Duncan EL.

Clin Endocrinol (Oxf). 2014 Jan;80(1):25-33. doi: 10.1111/cen.12331. Epub 2013 Oct 25.

PubMed [citation]
PMID:
24102379

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
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000763563.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

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 large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with pheochromocytoma (PMID: 24102379), head and neck paranglioma (PMID: 19351833, 23666964) and segregated with disease in an offspring of an individual affected with paraganglioma (PMID: 27279923). ClinVar contains an entry for this variant (Variation ID: 135194). Experimental in vitro studies in a yeast model system have shown that this missense change does not affect oxidative growth but it results in a partial reduction of SDH enzyme activity (PMID: 23175444). In summary, this variant is a rare missense change that has been reported in several affected individuals and partially affects SDH protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jul 7, 2021

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