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NM_000284.4(PDHA1):c.616G>A (p.Glu206Lys) AND Pyruvate dehydrogenase E1-alpha deficiency

Germline classification:
Pathogenic (1 submission)
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:
RCV003335884.1

Allele description [Variation Report for NM_000284.4(PDHA1):c.616G>A (p.Glu206Lys)]

NM_000284.4(PDHA1):c.616G>A (p.Glu206Lys)

Gene:
PDHA1:pyruvate dehydrogenase E1 subunit alpha 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp22.12
Genomic location:
Preferred name:
NM_000284.4(PDHA1):c.616G>A (p.Glu206Lys)
HGVS:
  • NC_000023.11:g.19355361G>A
  • NG_016781.1:g.16469G>A
  • NM_000284.4:c.616G>AMANE SELECT
  • NM_001173454.2:c.730G>A
  • NM_001173455.2:c.637G>A
  • NM_001173456.2:c.523G>A
  • NP_000275.1:p.Glu206Lys
  • NP_001166925.1:p.Glu244Lys
  • NP_001166926.1:p.Glu213Lys
  • NP_001166927.1:p.Glu175Lys
  • NC_000023.10:g.19373479G>A
  • NM_001173454.1:c.730G>A
Protein change:
E175K
Molecular consequence:
  • NM_000284.4:c.616G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173454.2:c.730G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173455.2:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173456.2:c.523G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Pyruvate dehydrogenase E1-alpha deficiency (PDHAD)
Synonyms:
X-linked Leigh syndrome; ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY; ATAXIA WITH LACTIC ACIDOSIS I; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010717; MedGen: C1839413; OMIM: 312170

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004046116Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenicgermlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot 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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046116.1

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

Description

This variant, also referred to as p.Glu206Lys due to use of an alternate transcript, has been previously reported as a heterozygous change in a female patient with clinical features of Pyruvate dehydrogenase deficiency (PMID: 19517265). A different missense variant involving the same amino acid position (p.Glu244Gln) has been reported in the literature however detailed clinical information was not provided (PMID: 29565416). Missense variants in neighboring residues have been reported in the Human Gene Mutation Database (PMID: 32596782). This variant is absent from the gnomAD population database and thus is presumed to be rare. In silico analyses support a deleterious effect of the c.730G>A (p.Glu244Lys) variant on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.730G>A (p.Glu244Lys) variant is classified as Pathogenic.

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

Last Updated: Oct 28, 2023