NM_003000.3(SDHB):c.689G>T (p.Arg230Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV000164275.8

Allele description [Variation Report for NM_003000.3(SDHB):c.689G>T (p.Arg230Leu)]

NM_003000.3(SDHB):c.689G>T (p.Arg230Leu)

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.689G>T (p.Arg230Leu)

HGVS:

NC_000001.11:g.17022684C>A
NG_012340.1:g.36487G>T
NM_003000.3:c.689G>TMANE SELECT
NP_002991.2:p.Arg230Leu
NP_002991.2:p.Arg230Leu
LRG_316t1:c.689G>T
LRG_316:g.36487G>T
LRG_316p1:p.Arg230Leu
NC_000001.10:g.17349179C>A
NM_003000.2:c.689G>T
p.R230L

Protein change:

R230L

Links:

dbSNP: rs587782604

NCBI 1000 Genomes Browser:

rs587782604

Molecular consequence:

NM_003000.3:c.689G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000214900	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18382370, 19351833, 23934599, 25791839, 27539324 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000214900

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Germline SDHB mutations are common in patients with apparently sporadic sympathetic paragangliomas.

Klein RD, Jin L, Rumilla K, Young WF Jr, Lloyd RV.

Diagn Mol Pathol. 2008 Jun;17(2):94-100. doi: 10.1097/PDM.0b013e318150d67c.

PubMed [citation]

PMID:: 18382370

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, et al.

Cancer Res. 2009 Apr 15;69(8):3650-6. doi: 10.1158/0008-5472.CAN-08-4057. Epub 2009 Apr 7.

PubMed [citation]

PMID:: 19351833

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000214900.9

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

Description

The p.R230L pathogenic mutation (also known as c.689G>T), located in coding exon 7 of the SDHB gene, results from a G to T substitution at nucleotide position 689. The arginine at codon 230 is replaced by leucine, an amino acid with dissimilar properties. This variant has been described in multiple unrelated individuals with extra-adrenal paragangliomas (Neumann HP et al. Cancer Res. 2009 Apr; 69(8):3650-6; Klein RD et al. Diagn. Mol. Pathol. 2008 Jun; 17(2):94-100; Jasperson KW et al. Fam. Cancer. 2013 Aug; Michaowska I et al. Neuroendocrinology. 2015 ; 101(4):321-30; Pandit R et al. Eur. J. Endocrinol. 2016 Oct;175:311-23). Two other alterations at the same codon, p.R230H (c.689G>A) and p.R230C (c.688C>T), have been detected in numerous individuals diagnosed with pheochromocytomas and/or paragangliomas (Gimenez-Roqueplo AP et al. Cancer Res. 2003 Sep 1;63(17):5615-21; Dahia PL et al. PLoS Genet. 2005 Jul;1(1):72-80; Neumann HP et al. Cancer Res. 2009 Apr 15;69(8):3650-6; Sevilla MA et al. Otolaryngol Head Neck Surg. 2009 May;140(5):724-9; Burnichon N et al. J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27; Cerecer-Gil et al. Clin Cancer Res 2010 Aug 15; 16(16):4148-54; Yang C et al. FASEB J. 2012 Nov;26(11):4506-16; Andrews KA et al. J. Med. Genet. 2018 Jun;55:384-394). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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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