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NM_003000.3(SDHB):c.728G>T (p.Cys243Phe) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 29, 2019
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:
RCV001026234.3

Allele description [Variation Report for NM_003000.3(SDHB):c.728G>T (p.Cys243Phe)]

NM_003000.3(SDHB):c.728G>T (p.Cys243Phe)

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.728G>T (p.Cys243Phe)
HGVS:
  • NC_000001.11:g.17022645C>A
  • NG_012340.1:g.36526G>T
  • NM_003000.3:c.728G>TMANE SELECT
  • NP_002991.2:p.Cys243Phe
  • LRG_316t1:c.728G>T
  • LRG_316:g.36526G>T
  • NC_000001.10:g.17349140C>A
  • NM_003000.2:c.728G>T
Protein change:
C243F
Links:
dbSNP: rs1570944788
NCBI 1000 Genomes Browser:
rs1570944788
Molecular consequence:
  • NM_003000.3:c.728G>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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001188575Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 29, 2019) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV001188575.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.C243F variant (also known as c.728G>T), located in coding exon 7 of the SDHB gene, results from a G to T substitution at nucleotide position 728. The cysteine at codon 243 is replaced by phenylalanine, an amino acid with highly dissimilar properties. Different alterations at the same position (p.C243R, p.C243S, and p.C243Y) have been identified in individuals with paraganglioma-pheochromocytoma (PGL-PCC) syndrome (Korpershoek E et al. Endocr. Relat. Cancer, 2007 Jun;14:453-62; Sue M et al. Eur. J. Endocrinol., 2015 Feb;172:89-95; Patócs A et al. Pathol. Oncol. Res., 2016 Oct;22:673-9; Ambry internal data). This cysteine residue acts as the 3Fe-4S ligand, and any missense substitution at this position is expected to prevent proper assembly of complex II (Iverson TM et al. J. Biol. Chem., 2012 Oct;287:35430-8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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 majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024