NM_000925.4(PDHB):c.478_479del (p.Gln160fs) AND Pyruvate dehydrogenase E1-beta deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 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:: RCV003819867.2

Allele description [Variation Report for NM_000925.4(PDHB):c.478_479del (p.Gln160fs)]

NM_000925.4(PDHB):c.478_479del (p.Gln160fs)

Gene:

PDHB:pyruvate dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

3p14.3

Genomic location:

Preferred name:

NM_000925.4(PDHB):c.478_479del (p.Gln160fs)

HGVS:

NC_000003.12:g.58430767TG[1]
NG_016860.1:g.8083CA[1]
NG_016860.2:g.8062CA[1]
NM_000925.4:c.478_479delMANE SELECT
NM_001173468.2:c.424_425del
NM_001315536.2:c.424_425del
NP_000916.2:p.Gln160fs
NP_001166939.1:p.Gln142fs
NP_001302465.1:p.Gln142fs
NC_000003.11:g.58416494TG[1]
NC_000003.11:g.58416494_58416495del
NR_033384.2:n.582CA[1]

Protein change:

Q142fs

Molecular consequence:

NM_000925.4:c.478_479del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173468.2:c.424_425del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001315536.2:c.424_425del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_033384.2:n.582CA[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004619497	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21914562, 25356417, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004619497

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV004619497.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln160Valfs*24) 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 has not been reported in the literature in individuals affected with PDHB-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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