NM_003000.3(SDHB):c.683_684del (p.Glu228fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 11, 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:: RCV000798175.6

Allele description [Variation Report for NM_003000.3(SDHB):c.683_684del (p.Glu228fs)]

NM_003000.3(SDHB):c.683_684del (p.Glu228fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.683_684del (p.Glu228fs)

HGVS:

NC_000001.11:g.17022689CT[1]
NG_012340.1:g.36479AG[1]
NM_003000.3:c.683_684delMANE SELECT
NP_002991.2:p.Glu228fs
LRG_316:g.36479AG[1]
NC_000001.10:g.17349184CT[1]
NC_000001.10:g.17349184_17349185del
NM_003000.2:c.683_684delAG
NM_003000.3:c.683_684del

Protein change:

E228fs

Links:

dbSNP: rs762812025

NCBI 1000 Genomes Browser:

rs762812025

Molecular consequence:

NM_003000.3:c.683_684del - 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
SCV000937776	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16912137, 24694336, 15328326, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000937776

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

germline

clinical testing

PubMed (4)
[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

High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing.

Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K.

J Clin Endocrinol Metab. 2006 Nov;91(11):4505-9. Epub 2006 Aug 15.

PubMed [citation]

PMID:: 16912137

Rare germline mutations identified by targeted next-generation sequencing of susceptibility genes in pheochromocytoma and paraganglioma.

Welander J, Andreasson A, Juhlin CC, Wiseman RW, Bäckdahl M, Höög A, Larsson C, Gimm O, Söderkvist P.

J Clin Endocrinol Metab. 2014 Jul;99(7):E1352-60. doi: 10.1210/jc.2013-4375. Epub 2014 Apr 2.

PubMed [citation]

PMID:: 24694336
PMCID:: PMC5393486

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000937776.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu228Glyfs*27) in the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the SDHB protein. This variant is present in population databases (rs762812025, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with malignant paraganglioma (PMID: 16912137, 24694336). ClinVar contains an entry for this variant (Variation ID: 438428). This variant disrupts a region of the SDHB protein in which other variant(s) (p.Ser239Tyrfs*8) have been determined to be pathogenic (PMID: 15328326; 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. 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: Sep 29, 2024

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