NM_003001.5(SDHC):c.387G>A (p.Trp129Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 9, 2021
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:: RCV001380749.6

Allele description [Variation Report for NM_003001.5(SDHC):c.387G>A (p.Trp129Ter)]

NM_003001.5(SDHC):c.387G>A (p.Trp129Ter)

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.387G>A (p.Trp129Ter)

HGVS:

NC_000001.11:g.161356822G>A
NG_012767.1:g.47447G>A
NM_001035511.3:c.242-5507G>A
NM_001035512.3:c.285G>A
NM_001035513.3:c.228G>A
NM_001278172.3:c.140-5507G>A
NM_001407115.1:c.507G>A
NM_001407116.1:c.330G>A
NM_001407117.1:c.324G>A
NM_001407118.1:c.279G>A
NM_001407119.1:c.276G>A
NM_001407120.1:c.276G>A
NM_001407121.1:c.185-5507G>A
NM_003001.5:c.387G>AMANE SELECT
NP_001030589.1:p.Trp95Ter
NP_001030590.1:p.Trp76Ter
NP_001394044.1:p.Trp169Ter
NP_001394045.1:p.Trp110Ter
NP_001394046.1:p.Trp108Ter
NP_001394047.1:p.Trp93Ter
NP_001394048.1:p.Trp92Ter
NP_001394049.1:p.Trp92Ter
NP_002992.1:p.Trp129Ter
NP_002992.1:p.Trp129Ter
LRG_317t1:c.387G>A
LRG_317:g.47447G>A
LRG_317p1:p.Trp129Ter
NC_000001.10:g.161326612G>A
NM_003001.3:c.387G>A
NR_103459.3:n.439G>A

Protein change:

W108*

Links:

dbSNP: rs981049067

NCBI 1000 Genomes Browser:

rs981049067

Molecular consequence:

NM_001035511.3:c.242-5507G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.140-5507G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407121.1:c.185-5507G>A - intron variant - [Sequence Ontology: SO:0001627]
NR_103459.3:n.439G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001035512.3:c.285G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001035513.3:c.228G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407115.1:c.507G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407116.1:c.330G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407117.1:c.324G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407118.1:c.279G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407119.1:c.276G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407120.1:c.276G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003001.5:c.387G>A - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001578906	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23083876, 24423348, 24758179, 27700540, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001578906

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 9, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer.

Ricketts CJ, Shuch B, Vocke CD, Metwalli AR, Bratslavsky G, Middelton L, Yang Y, Wei MH, Pautler SE, Peterson J, Stolle CA, Zbar B, Merino MJ, Schmidt LS, Pinto PA, Srinivasan R, Pacak K, Linehan WM.

J Urol. 2012 Dec;188(6):2063-71. doi: 10.1016/j.juro.2012.08.030. Epub 2012 Oct 18.

PubMed [citation]

PMID:: 23083876
PMCID:: PMC3856891

Phenotypic variability and risk of malignancy in SDHC-linked paragangliomas: lessons from three unrelated cases with an identical germline mutation (p.Arg133*).

Bickmann JK, Sollfrank S, Schad A, Musholt TJ, Springer E, Miederer M, Bartsch O, Papaspyrou K, Koutsimpelas D, Mann WJ, Weber MM, Lackner KJ, Rossmann H, Fottner C.

J Clin Endocrinol Metab. 2014 Mar;99(3):E489-96. doi: 10.1210/jc.2013-3486. Epub 2014 Jan 1.

PubMed [citation]

PMID:: 24423348

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001578906.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SDHC protein in which other variant(s) (p.Arg133*) have been determined to be pathogenic (PMID: 23083876, 24423348, 24758179, 27700540). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 428935). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp129*) in the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the SDHC protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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