NM_003000.2(SDHB):c.716C>G (p.Ser239Cys) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000795778.3

Allele description [Variation Report for NM_003000.2(SDHB):c.716C>G (p.Ser239Cys)]

NM_003000.2(SDHB):c.716C>G (p.Ser239Cys)

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_003000.2(SDHB):c.716C>G (p.Ser239Cys)
HGVS:
  • NC_000001.11:g.17022657G>C
  • NG_012340.1:g.36514C>G
  • NM_003000.2:c.716C>G
  • NP_002991.2:p.Ser239Cys
  • LRG_316t1:c.716C>G
  • LRG_316:g.36514C>G
  • LRG_316p1:p.Ser239Cys
  • NC_000001.10:g.17349152G>C
Protein change:
S239C
Links:
dbSNP: rs201098090
NCBI 1000 Genomes Browser:
rs201098090
Molecular consequence:
  • NM_003000.2:c.716C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gastrointestinal stromal tumor (GIST)
Synonyms:
Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723
Name:
Paragangliomas 4 (PGL4)
Synonyms:
CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Pheochromocytoma, extraadrenal and cervical paraganglioma; Paragangliomas, hereditary extraadrenal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310
Name:
Pheochromocytoma
Synonyms:
Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000935252Invitaecriteria provided, single submitter
Uncertain significance
(Jul 26, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Prevalence of germline mutations in patients with pheochromocytoma or abdominal paraganglioma and sporadic presentation: a population-based study in Western Sweden.

Muth A, Abel F, Jansson S, Nilsson O, Ahlman H, Wängberg B.

World J Surg. 2012 Jun;36(6):1389-94. doi: 10.1007/s00268-012-1430-6.

PubMed [citation]
PMID:
22270996
PMCID:
PMC3348434

Germline variants in cancer genes in high-risk non-BRCA patients from Puerto Rico.

Dutil J, Teer JK, Golubeva V, Yoder S, Tong WL, Arroyo N, Karam R, Echenique M, Matta JL, Monteiro AN.

Sci Rep. 2019 Nov 28;9(1):17769. doi: 10.1038/s41598-019-54170-6.

PubMed [citation]
PMID:
31780696
PMCID:
PMC6882826
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000935252.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces serine with cysteine at codon 239 of the SDHB protein (p.Ser239Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs201098090, ExAC 0.02%). This variant has been observed in individual(s) with pheochromocytoma and with breast cancer (PMID: 22270996, 31780696). ClinVar contains an entry for this variant (Variation ID: 161385). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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