NM_000018.4(ACADVL):c.1600G>A (p.Glu534Lys) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Conflicting interpretations of pathogenicity, Benign(5);Uncertain significance(1) (Last evaluated: Dec 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
7 submissions [Details]
Record status:
current
Accession:
RCV000020074.14

Allele description [Variation Report for NM_000018.4(ACADVL):c.1600G>A (p.Glu534Lys)]

NM_000018.4(ACADVL):c.1600G>A (p.Glu534Lys)

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.4(ACADVL):c.1600G>A (p.Glu534Lys)
Other names:
p.E534K:GAG>AAG; NM_000018.3(ACADVL):c.1600G>A(p.Glu534Lys); NM_001033859.2(ACADVL):c.1534G>A(p.Glu512Lys); NM_001270447.1(ACADVL):c.1669G>A(p.Glu557Lys); NM_001270448.1(ACADVL):c.1372G>A(p.Glu458Lys)
HGVS:
  • NC_000017.11:g.7224388G>A
  • NG_007975.1:g.9555G>A
  • NG_008391.2:g.663C>T
  • NG_033038.1:g.15157C>T
  • NM_000018.4:c.1600G>AMANE SELECT
  • NM_001033859.2:c.1534G>A
  • NM_001270447.1:c.1669G>A
  • NM_001270448.1:c.1372G>A
  • NP_000009.1:p.Glu534Lys
  • NP_000009.1:p.Glu534Lys
  • NP_000009.1:p.Glu534Lys
  • NP_000009.1:p.Glu534Lys
  • NP_001029031.1:p.Glu512Lys
  • NP_001257376.1:p.Glu557Lys
  • NP_001257377.1:p.Glu458Lys
  • NC_000017.10:g.7127707G>A
  • NM_000018.2:c.1600G>A
  • NM_000018.3:c.1600G>A
  • P49748:p.Glu534Lys
Protein change:
E458K
Links:
UniProtKB: P49748#VAR_010105; dbSNP: rs2230180
NCBI 1000 Genomes Browser:
rs2230180
Molecular consequence:
  • NM_000018.4:c.1600G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.2:c.1534G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.1:c.1669G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.1:c.1372G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (VLCAD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000602373ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Benign
(Nov 7, 2019)
germlineclinical testing

Citation Link,

SCV000654939Invitaecriteria provided, single submitter
Benign
(Dec 4, 2020)
germlineclinical testing

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

SCV000803496SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Uncertain significance
(May 31, 2018)
unknowncuration

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

SCV001140232Mendelicscriteria provided, single submitter
Benign
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001281708Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Apr 27, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001365184Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Benign
(Nov 1, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001459260Natera, Inc.no assertion criteria providedBenign
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing, curation

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

Carrier testing for severe childhood recessive diseases by next-generation sequencing.

Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, Langley RJ, Zhang L, Lee CC, Schilkey FD, Sheth V, Woodward JE, Peckham HE, Schroth GP, Kim RW, Kingsmore SF.

Sci Transl Med. 2011 Jan 12;3(65):65ra4. doi: 10.1126/scitranslmed.3001756.

PubMed [citation]
PMID:
21228398
PMCID:
PMC3740116
See all PubMed Citations (5)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000602373.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000654939.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From SIB Swiss Institute of Bioinformatics, SCV000803496.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Very long chain acyl-coa dehydrogenase deficiency, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.

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

From Mendelics, SCV001140232.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001281708.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365184.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The NM_000018.3:c.1600G>A (NP_000009.1:p.Glu534Lys) [GRCH38: NC_000017.11:g.7224388G>A] variant in ACADVL gene is interpretated to be Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BS1, BS2

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

From Natera, Inc., SCV001459260.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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