NM_003001.5(SDHC):c.397C>T (p.Arg133Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 24, 2024
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:: RCV000232178.18

Allele description [Variation Report for NM_003001.5(SDHC):c.397C>T (p.Arg133Ter)]

NM_003001.5(SDHC):c.397C>T (p.Arg133Ter)

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.397C>T (p.Arg133Ter)

HGVS:

NC_000001.11:g.161356832C>T
NG_012767.1:g.47457C>T
NM_001035511.3:c.242-5497C>T
NM_001035512.3:c.295C>T
NM_001035513.3:c.238C>T
NM_001278172.3:c.140-5497C>T
NM_001407115.1:c.517C>T
NM_001407116.1:c.340C>T
NM_001407117.1:c.334C>T
NM_001407118.1:c.289C>T
NM_001407119.1:c.286C>T
NM_001407120.1:c.286C>T
NM_001407121.1:c.185-5497C>T
NM_003001.5:c.397C>TMANE SELECT
NP_001030589.1:p.Arg99Ter
NP_001030590.1:p.Arg80Ter
NP_001394044.1:p.Arg173Ter
NP_001394045.1:p.Arg114Ter
NP_001394046.1:p.Arg112Ter
NP_001394047.1:p.Arg97Ter
NP_001394048.1:p.Arg96Ter
NP_001394049.1:p.Arg96Ter
NP_002992.1:p.Arg133Ter
NP_002992.1:p.Arg133Ter
LRG_317t1:c.397C>T
LRG_317:g.47457C>T
LRG_317p1:p.Arg133Ter
NC_000001.10:g.161326622C>T
NM_003001.3:c.397C>T
NR_103459.1:n.454C>T
NR_103459.3:n.449C>T
p.Arg133*
p.Arg133X
p.R133*

Protein change:

R112*

Links:

dbSNP: rs764575966

NCBI 1000 Genomes Browser:

rs764575966

Molecular consequence:

NM_001035511.3:c.242-5497C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.140-5497C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001407121.1:c.185-5497C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_103459.3:n.449C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001035512.3:c.295C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001035513.3:c.238C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407115.1:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407116.1:c.340C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407117.1:c.334C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407118.1:c.289C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407119.1:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407120.1:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003001.5:c.397C>T - 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
SCV000287802	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17898811, 23083876, 23282968, 24423348, 24523625, 24758179, 27700540, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000287802

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 24, 2024)

germline

clinical testing

PubMed (8)
[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

Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma.

Zbuk KM, Patocs A, Shealy A, Sylvester H, Miesfeldt S, Eng C.

Nat Clin Pract Oncol. 2007 Oct;4(10):608-12.

PubMed [citation]

PMID:: 17898811

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

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000287802.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Arg133*) in the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the SDHC protein. This variant is present in population databases (rs764575966, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with paragangliomas (PGLs) and gastrointestinal stromal tumor (PMID: 17898811, 23083876, 23282968, 24423348, 24523625, 24758179, 27700540). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 183753). Studies have shown that this premature translational stop signal is associated with inconclusive levels of altered splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.

#	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: May 1, 2024

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