NM_003001.5(SDHC):c.175del (p.Tyr59fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2020
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:: RCV001233063.8

Allele description [Variation Report for NM_003001.5(SDHC):c.175del (p.Tyr59fs)]

NM_003001.5(SDHC):c.175del (p.Tyr59fs)

Gene:

SDHC:succinate dehydrogenase complex subunit C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_003001.5(SDHC):c.175del (p.Tyr59fs)

HGVS:

NC_000001.11:g.161328493del
NG_012767.1:g.19118del
NM_001035511.3:c.175del
NM_001035512.3:c.77+4823del
NM_001035513.3:c.21-12101del
NM_001278172.3:c.77+4823del
NM_001407115.1:c.175del
NM_001407116.1:c.118del
NM_001407117.1:c.118del
NM_001407118.1:c.77+4823del
NM_001407119.1:c.64del
NM_001407120.1:c.64del
NM_001407121.1:c.118del
NM_003001.5:c.175delMANE SELECT
NP_001030588.1:p.Tyr59fs
NP_001394044.1:p.Tyr59fs
NP_001394045.1:p.Tyr40fs
NP_001394046.1:p.Tyr40fs
NP_001394048.1:p.Tyr22fs
NP_001394049.1:p.Tyr22fs
NP_001394050.1:p.Tyr40fs
NP_002992.1:p.Tyr59Thrfs
NP_002992.1:p.Tyr59fs
LRG_317t1:c.175del
LRG_317:g.19118del
NC_000001.10:g.161298283del
NM_003001.3:c.175del
NM_003001.3:c.175delT
NR_103459.3:n.200del

Protein change:

Y22fs

Links:

dbSNP: rs1671157149

NCBI 1000 Genomes Browser:

rs1671157149

Molecular consequence:

NM_001035511.3:c.175del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407115.1:c.175del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407116.1:c.118del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407117.1:c.118del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407119.1:c.64del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407120.1:c.64del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407121.1:c.118del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003001.5:c.175del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001035512.3:c.77+4823del - intron variant - [Sequence Ontology: SO:0001627]
NM_001035513.3:c.21-12101del - intron variant - [Sequence Ontology: SO:0001627]
NM_001278172.3:c.77+4823del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407118.1:c.77+4823del - intron variant - [Sequence Ontology: SO:0001627]
NR_103459.3:n.200del - 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

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Homo sapiens zinc finger protein 35 (clone HF.10) (ZNF35), mRNA
Homo sapiens zinc finger protein 35 (clone HF.10) (ZNF35), mRNA
gi|4508022|ref|NM_003420.1|

Nucleotide
protein FAM163A [Homo sapiens]
protein FAM163A [Homo sapiens]
gi|1046754183|ref|NP_001316645.1|

Protein
DC043512 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus lae...
DC043512 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus laevis cDNA clone xlk124k10ex 5', mRNA sequence
gi|118993093|gnl|dbEST|43293616|dbj 3512.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001405642	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19454582, 24758179, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001405642

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2020)

germline

clinical testing

PubMed (3)
[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

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP; PGL.NET network..

J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub 2009 May 19.

PubMed [citation]

PMID:: 19454582

The clinical phenotype of SDHC-associated hereditary paraganglioma syndrome (PGL3).

Else T, Marvin ML, Everett JN, Gruber SB, Arts HA, Stoffel EM, Auchus RJ, Raymond VM.

J Clin Endocrinol Metab. 2014 Aug;99(8):E1482-6. doi: 10.1210/jc.2013-3853. Epub 2014 Apr 23.

PubMed [citation]

PMID:: 24758179
PMCID:: PMC4121019

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001405642.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SDHC are known to be pathogenic (PMID: 19454582, 24758179). This variant has not been reported in the literature in individuals with SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr59Thrfs*20) in the SDHC gene. It is expected to result in an absent or disrupted protein product.

#	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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