NM_003000.3(SDHB):c.724C>T (p.Arg242Cys) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 29, 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:: RCV000461517.10

Allele description [Variation Report for NM_003000.3(SDHB):c.724C>T (p.Arg242Cys)]

NM_003000.3(SDHB):c.724C>T (p.Arg242Cys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.724C>T (p.Arg242Cys)

HGVS:

NC_000001.11:g.17022649G>A
NG_012340.1:g.36522C>T
NM_003000.3:c.724C>TMANE SELECT
NP_002991.2:p.Arg242Cys
NP_002991.2:p.Arg242Cys
LRG_316t1:c.724C>T
LRG_316:g.36522C>T
LRG_316p1:p.Arg242Cys
NC_000001.10:g.17349144G>A
NM_003000.2:c.724C>T
p.R242C

Protein change:

R242C

Links:

dbSNP: rs786203251

NCBI 1000 Genomes Browser:

rs786203251

Molecular consequence:

NM_003000.3:c.724C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000554036	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15235042, 17102086, 19802898, 22517554, 12000816, 19351833, 20208144, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000554036

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 2023)

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

The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features.

Badenhop RF, Jansen JC, Fagan PA, Lord RS, Wang ZG, Foster WJ, Schofield PR.

J Med Genet. 2004 Jul;41(7):e99. No abstract available.

PubMed [citation]

PMID:: 15235042
PMCID:: PMC1735850

Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas.

Schiavi F, Savvoukidis T, Trabalzini F, Grego F, Piazza M, Amistà P, Demattè S, Del Piano A, Cecchini ME, Erlic Z, De Lazzari P, Mantero F, Opocher G.

Ann N Y Acad Sci. 2006 Aug;1073:190-7.

PubMed [citation]

PMID:: 17102086

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000554036.8

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

Description

This missense change has been observed in individuals with hereditary paraganglioma or pheochromocytoma (PMID: 15235042, 17102086, 19351833, 19802898, 22517554). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 242 of the SDHB protein (p.Arg242Cys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 186827). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function. This variant disrupts the p.Arg242 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12000816, 19351833, 20208144). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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: Oct 13, 2024

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