U.S. flag

An official website of the United States government

NM_003001.5(SDHC):c.149G>A (p.Arg50His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 5, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000794964.11

Allele description [Variation Report for NM_003001.5(SDHC):c.149G>A (p.Arg50His)]

NM_003001.5(SDHC):c.149G>A (p.Arg50His)

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.149G>A (p.Arg50His)
HGVS:
  • NC_000001.11:g.161328467G>A
  • NG_012767.1:g.19092G>A
  • NM_001035511.3:c.149G>A
  • NM_001035512.3:c.77+4797G>A
  • NM_001035513.3:c.21-12127G>A
  • NM_001278172.3:c.77+4797G>A
  • NM_001407115.1:c.149G>A
  • NM_001407116.1:c.92G>A
  • NM_001407117.1:c.92G>A
  • NM_001407118.1:c.77+4797G>A
  • NM_001407119.1:c.38G>A
  • NM_001407120.1:c.38G>A
  • NM_001407121.1:c.92G>A
  • NM_003001.5:c.149G>AMANE SELECT
  • NP_001030588.1:p.Arg50His
  • NP_001394044.1:p.Arg50His
  • NP_001394045.1:p.Arg31His
  • NP_001394046.1:p.Arg31His
  • NP_001394048.1:p.Arg13His
  • NP_001394049.1:p.Arg13His
  • NP_001394050.1:p.Arg31His
  • NP_002992.1:p.Arg50His
  • NP_002992.1:p.Arg50His
  • LRG_317t1:c.149G>A
  • LRG_317:g.19092G>A
  • LRG_317p1:p.Arg50His
  • NC_000001.10:g.161298257G>A
  • NM_003001.3:c.149G>A
  • NR_103459.3:n.174G>A
Protein change:
R13H
Links:
dbSNP: rs769177037
NCBI 1000 Genomes Browser:
rs769177037
Molecular consequence:
  • NM_001035512.3:c.77+4797G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001035513.3:c.21-12127G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001278172.3:c.77+4797G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407118.1:c.77+4797G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001035511.3:c.149G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407115.1:c.149G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407116.1:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407117.1:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407119.1:c.38G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407120.1:c.38G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407121.1:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003001.5:c.149G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_103459.3:n.174G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Gastrointestinal stromal tumor
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 3 (PPGL3)
Synonyms:
GLOMUS TUMORS, FAMILIAL, 3; SDHC-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 3); PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 3
Identifiers:
MONDO: MONDO:0011544; MedGen: C1854336; Orphanet: 29072; OMIM: 605373

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000934402Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 5, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot 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

A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma.

Rattenberry E, Vialard L, Yeung A, Bair H, McKay K, Jafri M, Canham N, Cole TR, Denes J, Hodgson SV, Irving R, Izatt L, Korbonits M, Kumar AV, Lalloo F, Morrison PJ, Woodward ER, Macdonald F, Wallis Y, Maher ER.

J Clin Endocrinol Metab. 2013 Jul;98(7):E1248-56. doi: 10.1210/jc.2013-1319. Epub 2013 May 10.

PubMed [citation]
PMID:
23666964
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000934402.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg50 amino acid residue in SDHC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19351833, 23666964, 24102379, 27279923). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 641671). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is present in population databases (rs769177037, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 50 of the SDHC protein (p.Arg50His).

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

Last Updated: Jan 13, 2025