NM_000018.4(ACADVL):c.520G>A (p.Val174Met) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Apr 9, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000179696.4

Allele description [Variation Report for NM_000018.4(ACADVL):c.520G>A (p.Val174Met)]

NM_000018.4(ACADVL):c.520G>A (p.Val174Met)

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.520G>A (p.Val174Met)
HGVS:
  • NC_000017.11:g.7221580G>A
  • NG_007975.1:g.6747G>A
  • NM_000018.4:c.520G>A
  • NM_001270448.1:c.292G>A
  • NP_000009.1:p.Val174Met
  • NP_001257377.1:p.Val98Met
  • NC_000017.10:g.7124899G>A
  • NM_000018.2:c.520G>A
  • NM_000018.3:c.520G>A
  • P49748:p.Val174Met
Protein change:
V174M
Links:
UniProtKB: P49748#VAR_000334; dbSNP: rs369560930
NCBI 1000 Genomes Browser:
rs369560930
Molecular consequence:
  • NM_000018.3:c.520G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000231986EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Mar 23, 2015)
germlineclinical testing

Citation Link,

SCV000486666Counsylcriteria provided, single submitter
Likely pathogenic
(Jul 21, 2016)
unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000773888Invitaecriteria provided, single submitter
Likely pathogenic
(Apr 9, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown4not providednot providednot providednot providedclinical testing

Citations

PubMed

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N.

Am J Hum Genet. 1999 Feb;64(2):479-94.

PubMed [citation]
PMID:
9973285
PMCID:
PMC1377757

Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

Gobin-Limballe S, McAndrew RP, Djouadi F, Kim JJ, Bastin J.

Biochim Biophys Acta. 2010 May;1802(5):478-84. doi: 10.1016/j.bbadis.2010.01.001. Epub 2010 Jan 12.

PubMed [citation]
PMID:
20060901
PMCID:
PMC3401415
See all PubMed Citations (7)

Details of each submission

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000231986.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided4not providednot providednot provided

From Counsyl, SCV000486666.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000773888.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces valine with methionine at codon 174 of the ACADVL protein (p.Val174Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs369560930, ExAC 0.01%). This variant has been reported as homozygous or in combination with another ACADVL variant in several individuals affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 17999356, 18670371, 23430950, 26881790). This variant is also known as p.Val134Met in the literature.  ClinVar contains an entry for this variant (Variation ID: 92286). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Apr 19, 2019

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