NM_006859.4(LIAS):c.1113C>A (p.Asp371Glu) AND Pyruvate dehydrogenase lipoic acid synthetase deficiency

Clinical significance:Uncertain significance (Last evaluated: Jan 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001209131.2

Allele description [Variation Report for NM_006859.4(LIAS):c.1113C>A (p.Asp371Glu)]

NM_006859.4(LIAS):c.1113C>A (p.Asp371Glu)

Gene:
LIAS:lipoic acid synthetase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p14
Genomic location:
Preferred name:
NM_006859.4(LIAS):c.1113C>A (p.Asp371Glu)
HGVS:
  • NC_000004.12:g.39477109C>A
  • NG_032111.1:g.23065C>A
  • NM_001278590.2:c.984C>A
  • NM_001363700.2:c.804C>A
  • NM_006859.4:c.1113C>AMANE SELECT
  • NM_194451.3:c.*32C>A
  • NP_001265519.1:p.Asp328Glu
  • NP_001350629.1:p.Asp268Glu
  • NP_006850.2:p.Asp371Glu
  • NC_000004.11:g.39478729C>A
  • NM_006859.3:c.1113C>A
Protein change:
D268E
Molecular consequence:
  • NM_194451.3:c.*32C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001278590.2:c.984C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363700.2:c.804C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006859.4:c.1113C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Pyruvate dehydrogenase lipoic acid synthetase deficiency (HGCLAS)
Synonyms:
HYPERGLYCINEMIA, LACTIC ACIDOSIS, AND SEIZURES
Identifiers:
MONDO: MONDO:0013762; MedGen: C3280887; Orphanet: 401859; OMIM: 614462

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001380553Invitaecriteria provided, single submitter
Uncertain significance
(Jan 21, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001380553.2

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

Description

This sequence change replaces aspartic acid with glutamic acid at codon 371 of the LIAS protein (p.Asp371Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LIAS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Apr 12, 2021

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