NM_001931.5(DLAT):c.1664C>A (p.Pro555Gln) AND Pyruvate dehydrogenase E2 deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 2021
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:: RCV001867039.3

Allele description [Variation Report for NM_001931.5(DLAT):c.1664C>A (p.Pro555Gln)]

NM_001931.5(DLAT):c.1664C>A (p.Pro555Gln)

Genes:

PIH1D2:PIH1 domain containing 2 [Gene - HGNC]
DLAT:dihydrolipoamide S-acetyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_001931.5(DLAT):c.1664C>A (p.Pro555Gln)

HGVS:

NC_000011.10:g.112060052C>A
NG_013342.1:g.40239C>A
NM_001372031.1:c.1682C>A
NM_001372032.1:c.1658C>A
NM_001372033.1:c.1643C>A
NM_001372034.1:c.1631C>A
NM_001372035.1:c.1556C>A
NM_001372036.1:c.1538C>A
NM_001372037.1:c.1496C>A
NM_001372038.1:c.1385C>A
NM_001372039.1:c.1349C>A
NM_001372040.1:c.1283C>A
NM_001372041.1:c.1241C>A
NM_001372042.1:c.1202C>A
NM_001931.5:c.1664C>AMANE SELECT
NP_001358960.1:p.Pro561Gln
NP_001358961.1:p.Pro553Gln
NP_001358962.1:p.Pro548Gln
NP_001358963.1:p.Pro544Gln
NP_001358964.1:p.Pro519Gln
NP_001358965.1:p.Pro513Gln
NP_001358966.1:p.Pro499Gln
NP_001358967.1:p.Pro462Gln
NP_001358968.1:p.Pro450Gln
NP_001358969.1:p.Pro428Gln
NP_001358970.1:p.Pro414Gln
NP_001358971.1:p.Pro401Gln
NP_001922.2:p.Pro555Gln
NC_000011.9:g.111930776C>A
NR_164072.1:n.1541C>A

Protein change:

P401Q

Links:

dbSNP: rs1864460439

NCBI 1000 Genomes Browser:

rs1864460439

Molecular consequence:

NM_001372031.1:c.1682C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372032.1:c.1658C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372033.1:c.1643C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372034.1:c.1631C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372035.1:c.1556C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372036.1:c.1538C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372037.1:c.1496C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372038.1:c.1385C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372039.1:c.1349C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372040.1:c.1283C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372041.1:c.1241C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372042.1:c.1202C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001931.5:c.1664C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164072.1:n.1541C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Pyruvate dehydrogenase E2 deficiency (PDHDD)
Synonyms:: LACTIC ACIDEMIA DUE TO DEFECT OF E2 LIPOYL TRANSACETYLASE OF THE PYRUVATE DEHYDROGENASE COMPLEX; Dihydrolipoamide Acetyltransferase (E2) Deficiency
Identifiers:: MONDO: MONDO:0009502; MedGen: C1855565; Orphanet: 765; Orphanet: 79244; OMIM: 245348

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002119314	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002119314

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002119314.2

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

Description

This sequence change replaces proline with glutamine at codon 555 of the DLAT protein (p.Pro555Gln). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DLAT-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DLAT protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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