NM_001931.5(DLAT):c.436G>A (p.Ala146Thr) AND Pyruvate dehydrogenase E2 deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 8, 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:: RCV001931286.2

Allele description

NM_001931.5(DLAT):c.436G>A (p.Ala146Thr)

Gene:

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.436G>A (p.Ala146Thr)

HGVS:

NC_000011.10:g.112028569G>A
NG_013342.1:g.8756G>A
NM_001372031.1:c.436G>A
NM_001372032.1:c.436G>A
NM_001372033.1:c.436G>A
NM_001372034.1:c.403G>A
NM_001372035.1:c.436G>A
NM_001372036.1:c.310G>A
NM_001372037.1:c.268G>A
NM_001372038.1:c.381+2270G>A
NM_001372039.1:c.436G>A
NM_001372040.1:c.364+2287G>A
NM_001372041.1:c.436G>A
NM_001372042.1:c.-31G>A
NM_001931.5:c.436G>AMANE SELECT
NP_001358960.1:p.Ala146Thr
NP_001358961.1:p.Ala146Thr
NP_001358962.1:p.Ala146Thr
NP_001358963.1:p.Ala135Thr
NP_001358964.1:p.Ala146Thr
NP_001358965.1:p.Ala104Thr
NP_001358966.1:p.Ala90Thr
NP_001358968.1:p.Ala146Thr
NP_001358970.1:p.Ala146Thr
NP_001922.2:p.Ala146Thr
NC_000011.9:g.111899293G>A
NR_164072.1:n.501G>A

Protein change:

A104T

Links:

dbSNP: rs1201600211

NCBI 1000 Genomes Browser:

rs1201600211

Molecular consequence:

NM_001372042.1:c.-31G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001372038.1:c.381+2270G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001372040.1:c.364+2287G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001372031.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372032.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372033.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372034.1:c.403G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372035.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372036.1:c.310G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372037.1:c.268G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372039.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001372041.1:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001931.5:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164072.1:n.501G>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
SCV002197978	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 8, 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

SCV002197978

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 8, 2021)

germline

clinical testing

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

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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 Invitae, SCV002197978.2

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 146 of the DLAT protein (p.Ala146Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DLAT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Dec 24, 2023

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