NM_003000.3(SDHB):c.654G>C (p.Trp218Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 8, 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:: RCV004366668.1

Allele description [Variation Report for NM_003000.3(SDHB):c.654G>C (p.Trp218Cys)]

NM_003000.3(SDHB):c.654G>C (p.Trp218Cys)

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.654G>C (p.Trp218Cys)

HGVS:

NC_000001.11:g.17022719C>G
NG_012340.1:g.36452G>C
NM_001407361.1:c.600G>C
NM_003000.3:c.654G>CMANE SELECT
NP_001394290.1:p.Trp200Cys
NP_002991.2:p.Trp218Cys
NP_002991.2:p.Trp218Cys
LRG_316t1:c.654G>C
LRG_316:g.36452G>C
LRG_316p1:p.Trp218Cys
NC_000001.10:g.17349214C>G
NM_003000.2:c.654G>C

Protein change:

W200C

Molecular consequence:

NM_001407361.1:c.600G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003000.3:c.654G>C - 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
SCV005020182	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 8, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005020182

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 8, 2024)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV005020182.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.W218C variant (also known as c.654G>C), located in coding exon 7 of the SDHB gene, results from a G to C substitution at nucleotide position 654. The tryptophan at codon 218 is replaced by cysteine, an amino acid with highly dissimilar properties. Another alteration at the same codon, p.W218S (c.653G>C), has been identified in multiple individuals with paragangliomas (Bayley JP et al. BMC Med. Genet., 2006 Jan;7:1). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be 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: Sep 29, 2024

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