NM_003000.3(SDHB):c.572G>A (p.Cys191Tyr) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Oct 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001387122.1

Allele description [Variation Report for NM_003000.3(SDHB):c.572G>A (p.Cys191Tyr)]

NM_003000.3(SDHB):c.572G>A (p.Cys191Tyr)

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.572G>A (p.Cys191Tyr)
HGVS:
  • NC_000001.11:g.17024043C>T
  • NG_012340.1:g.35128G>A
  • NM_003000.3:c.572G>AMANE SELECT
  • NP_002991.2:p.Cys191Tyr
  • LRG_316t1:c.572G>A
  • LRG_316:g.35128G>A
  • NC_000001.10:g.17350538C>T
  • NM_003000.2:c.572G>A
Protein change:
C191Y
Links:
Molecular consequence:
  • NM_003000.3:c.572G>A - 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
SCV001587662Invitaecriteria provided, single submitter
Pathogenic
(Oct 16, 2020)
germlineclinical testing

PubMed (5)
[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

SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T).

Papathomas TG, Oudijk L, Persu A, Gill AJ, van Nederveen F, Tischler AS, Tissier F, Volante M, Matias-Guiu X, Smid M, Favier J, Rapizzi E, Libe R, Currás-Freixes M, Aydin S, Huynh T, Lichtenauer U, van Berkel A, Canu L, Domingues R, Clifton-Bligh RJ, Bialas M, et al.

Mod Pathol. 2015 Jun;28(6):807-21. doi: 10.1038/modpathol.2015.41. Epub 2015 Feb 27.

PubMed [citation]
PMID:
25720320

Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients.

Piccini V, Rapizzi E, Bacca A, Di Trapani G, Pulli R, Giachè V, Zampetti B, Lucci-Cordisco E, Canu L, Corsini E, Faggiano A, Deiana L, Carrara D, Tantardini V, Mariotti S, Ambrosio MR, Zatelli MC, Parenti G, Colao A, Pratesi C, Bernini G, Ercolino T, et al.

Endocr Relat Cancer. 2012 Apr 10;19(2):149-55. doi: 10.1530/ERC-11-0369. Print 2012 Apr.

PubMed [citation]
PMID:
22241717
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001587662.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces cysteine with tyrosine at codon 191 of the SDHB protein (p.Cys191Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with paraganglioma and pheochromocytoma (PMID: 19261679, 25720320, 22241717, 30050099). ClinVar contains an entry for this variant (Variation ID: 976001). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHB protein function. This variant has been reported to affect SDHB protein function (PMID: 19261679). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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