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NM_003000.3(SDHB):c.143A>T (p.Asp48Val) AND Paragangliomas 4

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 7, 2023
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:
RCV003315403.3

Allele description [Variation Report for NM_003000.3(SDHB):c.143A>T (p.Asp48Val)]

NM_003000.3(SDHB):c.143A>T (p.Asp48Val)

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.143A>T (p.Asp48Val)
HGVS:
  • NC_000001.11:g.17044818T>A
  • NG_012340.1:g.14353A>T
  • NM_003000.3:c.143A>TMANE SELECT
  • NP_002991.2:p.Asp48Val
  • NP_002991.2:p.Asp48Val
  • LRG_316t1:c.143A>T
  • LRG_316:g.14353A>T
  • LRG_316p1:p.Asp48Val
  • NC_000001.10:g.17371313T>A
  • NM_003000.2:c.143A>T
Protein change:
D48V; ASP48VAL
Links:
OMIM: 185470.0020; dbSNP: rs202101384
NCBI 1000 Genomes Browser:
rs202101384
Molecular consequence:
  • NM_003000.3:c.143A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Paragangliomas 4 (PPGL4)
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004015257KCCC/NGS Laboratory, Kuwait Cancer Control Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jul 7, 2023)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015257.1

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

Description

This sequence change replaces aspartic acid with valine at codon 48 of the SDHB protein (p.Asp48Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs202101384, ExAC 0.04%). This variant has been observed as homozygous or in combination with other SDHB variant in individuals affected with autosomal recessive mitochondrial complex II deficiency (PMID: 22972948, 27556822, 29282712, 26642834, 27159321, 26968897, 27604842, 23174333, 29019354, 34426522, 31589614, 33726816, 26925370). However, this variant has not been observed in individuals with pheochromocytoma (PCC) or paraganglioma (PGL). ClinVar contains an entry for this variant (Variation ID: 39584). In silico analysis supports that this missense variant has a deleterious effect on protein structure/function also an experimental study shown the affected protein function . In summary, this variant has been observed in individuals with mitochondrial complex II deficiency and has been shown to affect protein function. The currently available evidence indicates that the variant is pathogenic, Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jun 17, 2024