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NM_000925.4(PDHB):c.495G>A (p.Trp165Ter) AND Pyruvate dehydrogenase E1-beta deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 24, 2024
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:
RCV003627667.2

Allele description [Variation Report for NM_000925.4(PDHB):c.495G>A (p.Trp165Ter)]

NM_000925.4(PDHB):c.495G>A (p.Trp165Ter)

Gene:
PDHB:pyruvate dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p14.3
Genomic location:
Preferred name:
NM_000925.4(PDHB):c.495G>A (p.Trp165Ter)
HGVS:
  • NC_000003.12:g.58430751C>T
  • NG_016860.1:g.8102G>A
  • NG_016860.2:g.8081G>A
  • NM_000925.4:c.495G>AMANE SELECT
  • NM_001173468.2:c.441G>A
  • NM_001315536.2:c.441G>A
  • NP_000916.2:p.Trp165Ter
  • NP_001166939.1:p.Trp147Ter
  • NP_001302465.1:p.Trp147Ter
  • NC_000003.11:g.58416478C>T
  • NR_033384.2:n.601G>A
Protein change:
W147*
Molecular consequence:
  • NR_033384.2:n.601G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000925.4:c.495G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001173468.2:c.441G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001315536.2:c.441G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Pyruvate dehydrogenase E1-beta deficiency (PDHBD)
Identifiers:
MONDO: MONDO:0013580; MedGen: C3279841; Orphanet: 255138; Orphanet: 765; OMIM: 614111

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004396317Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 24, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein.

Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M.

Mol Genet Metab. 2011 Dec;104(4):507-16. doi: 10.1016/j.ymgme.2011.08.008. Epub 2011 Aug 18.

PubMed [citation]
PMID:
21914562

Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects.

Ferriero R, Boutron A, Brivet M, Kerr D, Morava E, Rodenburg RJ, Bonafé L, Baumgartner MR, Anikster Y, Braverman NE, Brunetti-Pierri N.

Ann Clin Transl Neurol. 2014 Jul;1(7):462-70. doi: 10.1002/acn3.73. Epub 2014 Jun 19.

PubMed [citation]
PMID:
25356417
PMCID:
PMC4184775
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004396317.1

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

Description

This sequence change creates a premature translational stop signal (p.Trp165*) in the PDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDHB are known to be pathogenic (PMID: 21914562, 25356417). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PDHB-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Sep 29, 2024