NM_003000.3(SDHB):c.686_687dup (p.Arg230fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 10, 2022
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:: RCV003103339.3

Allele description [Variation Report for NM_003000.3(SDHB):c.686_687dup (p.Arg230fs)]

NM_003000.3(SDHB):c.686_687dup (p.Arg230fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.686_687dup (p.Arg230fs)

HGVS:

NC_000001.11:g.17022687_17022688dup
NG_012340.1:g.36484_36485dup
NM_001407361.1:c.631_632dup
NM_003000.3:c.686_687dupMANE SELECT
NP_001394290.1:p.Arg212Serfs
NP_002991.2:p.Arg230Serfs
NP_002991.2:p.Arg230fs
LRG_316t1:c.685_686dup
LRG_316:g.36484_36485dup
LRG_316p1:p.Arg230Serfs
NC_000001.10:g.17349180_17349181insCT
NC_000001.10:g.17349182_17349183dup
NM_003000.2:c.685_686dup
NM_003000.2:c.686_687dupAG

Protein change:

R230fs

Molecular consequence:

NM_001407361.1:c.631_632dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003000.3:c.686_687dup - 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
SCV003452117	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 10, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15328326, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003452117

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 10, 2022)

germline

clinical testing

PubMed (2)
[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

Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.

Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C; European-American Paraganglioma Study Group..

JAMA. 2004 Aug 25;292(8):943-51. Erratum in: JAMA. 2004 Oct 13;292(14):1686.

PubMed [citation]

PMID:: 15328326

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003452117.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Arg230Serfs*19) in the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the SDHB protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. 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: May 12, 2024

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