NM_003000.3(SDHB):c.713del (p.Phe238fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 12, 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:: RCV001233559.5

Allele description [Variation Report for NM_003000.3(SDHB):c.713del (p.Phe238fs)]

NM_003000.3(SDHB):c.713del (p.Phe238fs)

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.713del (p.Phe238fs)

HGVS:

NC_000001.11:g.17022661del
NG_012340.1:g.36511del
NM_003000.3:c.713delMANE SELECT
NP_002991.2:p.Phe238fs
NP_002991.2:p.Phe238fs
LRG_316t1:c.713del
LRG_316:g.36511del
LRG_316p1:p.Phe238fs
NC_000001.10:g.17349155del
NC_000001.10:g.17349156del
NM_003000.2:c.713del
NM_003000.2:c.713delT

Protein change:

F238fs

Links:

dbSNP: rs876660642

NCBI 1000 Genomes Browser:

rs876660642

Molecular consequence:

NM_003000.3:c.713del - frameshift variant - [Sequence Ontology: SO:0001589]

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 4 (PPGL4)
Synonyms:: CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Pheochromocytoma, extraadrenal and cervical paraganglioma; Paragangliomas, hereditary extraadrenal; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310

Name:: Pheochromocytoma
Synonyms:: Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001406160	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16317055, 19454582, 22517554, 28490599, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001406160

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2023)

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

Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.

Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG.

J Clin Endocrinol Metab. 2006 Mar;91(3):827-36. Epub 2005 Nov 29.

PubMed [citation]

PMID:: 16317055

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001406160.4

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

Description

This variant is also known as c.713delT (p.Phe238fs). This premature translational stop signal has been observed in individual(s) with paraganglioma-pheochromocytoma syndromes (PMID: 16317055, 19454582, 22517554, 28490599). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Phe238Serfs*10) in the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 43 amino acid(s) of the SDHB protein. ClinVar contains an entry for this variant (Variation ID: 233795). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SDHB protein in which other variant(s) (p.Leu240Serfs*16) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.

#	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 12, 2024

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