NM_003000.3(SDHB):c.167C>T (p.Pro56Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 26, 2024
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:: RCV004508359.1

Allele description [Variation Report for NM_003000.3(SDHB):c.167C>T (p.Pro56Leu)]

NM_003000.3(SDHB):c.167C>T (p.Pro56Leu)

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.167C>T (p.Pro56Leu)

HGVS:

NC_000001.11:g.17044794G>A
NG_012340.1:g.14377C>T
NM_001407361.1:c.167C>T
NM_003000.3:c.167C>TMANE SELECT
NP_001394290.1:p.Pro56Leu
NP_002991.2:p.Pro56Leu
NP_002991.2:p.Pro56Leu
LRG_316t1:c.167C>T
LRG_316:g.14377C>T
LRG_316p1:p.Pro56Leu
NC_000001.10:g.17371289G>A
NM_003000.2:c.167C>T

Protein change:

P56L

Molecular consequence:

NM_001407361.1:c.167C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003000.3:c.167C>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

Recent activity

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Chain M, V-type proton ATPase subunit G 1
Chain M, V-type proton ATPase subunit G 1
gi|2289002190|pdb|7U4T|M

Protein
Chain J, V-type proton ATPase subunit E 1
Chain J, V-type proton ATPase subunit E 1
gi|2289002189|pdb|7U4T|J

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005019672	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 26, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16317055, 19454582 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005019672

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 26, 2024)

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

Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.

Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG.

J Clin Endocrinol Metab. 2006 Mar;91(3):827-36. Epub 2005 Nov 29.

PubMed [citation]

PMID:: 16317055

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

Details of each submission

From Ambry Genetics, SCV005019672.1

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

Description

The p.P56L variant (also known as c.167C>T), located in coding exon 2 of the SDHB gene, results from a C to T substitution at nucleotide position 167. The proline at codon 56 is replaced by leucine, an amino acid with similar properties. This variant was reported in multiple individuals with features consistent with SDHB-related paraganglioma-pheochromocytoma syndrome (Benn DE et al. J Clin Endocrinol Metab, 2006 Mar;91:827-36; Burnichon N et al. J Clin Endocrinol Metab, 2009 Aug;94:2817-27). 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 available evidence, 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: May 7, 2024

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