NM_003000.2(SDHB):c.23C>T (p.Ser8Phe) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Apr 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000687472.4

Allele description [Variation Report for NM_003000.2(SDHB):c.23C>T (p.Ser8Phe)]

NM_003000.2(SDHB):c.23C>T (p.Ser8Phe)

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.23C>T (p.Ser8Phe)
HGVS:
  • NC_000001.11:g.17053997G>A
  • NG_012340.1:g.5174C>T
  • NM_003000.2:c.23C>T
  • NP_002991.2:p.Ser8Phe
  • LRG_316t1:c.23C>T
  • LRG_316:g.5174C>T
  • LRG_316p1:p.Ser8Phe
  • NC_000001.10:g.17380492G>A
Protein change:
S8F
Links:
dbSNP: rs199848267
NCBI 1000 Genomes Browser:
rs199848267
Molecular consequence:
  • NM_003000.2:c.23C>T - 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
SCV000815037Invitaecriteria provided, single submitter
Uncertain significance
(Apr 20, 2020)
germlineclinical testing

PubMed (2)
[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

Genetic mutation screening in an italian cohort of nonsyndromic pheochromocytoma/paraganglioma patients.

Castellano M, Mori L, Giacchè M, Agliozzo E, Tosini R, Panarotto A, Cappelli C, Mulatero P, Cumetti D, Veglio F, Agabiti-Rosei E.

Ann N Y Acad Sci. 2006 Aug;1073:156-65.

PubMed [citation]
PMID:
17102082

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000815037.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces serine with phenylalanine at codon 8 of the SDHB protein (p.Ser8Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs199848267, ExAC 0.003%). This variant has been reported in an individual affected with para-adrenal paraganglioma. (PMID: 17102082). 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 tolerated, 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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