NM_003000.3(SDHB):c.763A>G (p.Lys255Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 26, 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:: RCV004028790.1

Allele description [Variation Report for NM_003000.3(SDHB):c.763A>G (p.Lys255Glu)]

NM_003000.3(SDHB):c.763A>G (p.Lys255Glu)

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.763A>G (p.Lys255Glu)

HGVS:

NC_000001.11:g.17022610T>C
NG_012340.1:g.36561A>G
NM_003000.3:c.763A>GMANE SELECT
NP_002991.2:p.Lys255Glu
NP_002991.2:p.Lys255Glu
LRG_316t1:c.763A>G
LRG_316:g.36561A>G
LRG_316p1:p.Lys255Glu
NC_000001.10:g.17349105T>C
NM_003000.2:c.763A>G

Protein change:

K255E

Links:

dbSNP: rs1570944737

NCBI 1000 Genomes Browser:

rs1570944737

Molecular consequence:

NM_003000.3:c.763A>G - 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
SCV005019712	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19454582, 34906457 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005019712

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 26, 2023)

germline

clinical testing

PubMed (2)
[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

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

Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.

Garrett A, Loveday C, King L, Butler S, Robinson R, Horton C, Yussuf A, Choi S, Torr B, Durkie M, Burghel GJ, Drummond J, Berry I, Wallace A, Callaway A, Eccles D, Tischkowitz M, Tatton-Brown K, Snape K, McVeigh T, Izatt L, Woodward ER, et al.

Genet Med. 2022 Jan;24(1):41-50. doi: 10.1016/j.gim.2021.08.004. Epub 2021 Nov 30.

PubMed [citation]

PMID:: 34906457
PMCID:: PMC8759765

Details of each submission

From Ambry Genetics, SCV005019712.1

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

Description

The p.K255E variant (also known as c.763A>G), located in coding exon 7 of the SDHB gene, results from an A to G substitution at nucleotide position 763. The lysine at codon 255 is replaced by glutamic acid, an amino acid with similar properties. This variant has been reported in paraganglioma/pheochromocytoma cohorts (Burnichon N et al. J Clin Endocrinol Metab, 2009 Aug;94:2817-27; Garrett A et al. Genet Med, 2022 Jan;24:41-50). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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