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NM_000284.4(PDHA1):c.650C>T (p.Pro217Leu) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 12, 2018
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:
RCV000494486.2

Allele description [Variation Report for NM_000284.4(PDHA1):c.650C>T (p.Pro217Leu)]

NM_000284.4(PDHA1):c.650C>T (p.Pro217Leu)

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.650C>T (p.Pro217Leu)
HGVS:
  • NC_000023.11:g.19355395C>T
  • NG_016781.1:g.16503C>T
  • NM_000284.4:c.650C>TMANE SELECT
  • NM_001173454.2:c.764C>T
  • NM_001173455.2:c.671C>T
  • NM_001173456.2:c.557C>T
  • NP_000275.1:p.Pro217Leu
  • NP_001166925.1:p.Pro255Leu
  • NP_001166926.1:p.Pro224Leu
  • NP_001166927.1:p.Pro186Leu
  • NC_000023.10:g.19373513C>T
  • NM_000284.3:c.650C>T
Protein change:
P186L
Links:
dbSNP: rs1131691792
NCBI 1000 Genomes Browser:
rs1131691792
Molecular consequence:
  • NM_000284.4:c.650C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173454.2:c.764C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173455.2:c.671C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173456.2:c.557C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000582844GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Apr 12, 2018) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000582844.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The P217L variant has been reported, using alternate nomenclature as P188L, in a male with pyruvate dehydrogenase deficiency who had decreased amounts of the E1 subunit of the pyruvate dehydrogenase enzyme in multiple tissues (Hemalatha et al. 1995). Expression of P217L in E coli resulted in no residual enzyme compared to wild-type (Tripatara et al. 1999). P188 is reported to be located between the alpha-helix and beta-sheet of the thiamin pyrophosphate (TPP)-binding motif and is predicted to be crucial for the formation of the TPP-binding cleft (Tripatara et al. 1999). The P217L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P217L variant is a semi-conservative amino acid substitution. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret this variant as pathogenic.

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

Last Updated: Apr 23, 2022