NM_000018.3(ACADVL):c.865G>A (p.Gly289Arg) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Apr 2, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000408960.2

Allele description [Variation Report for NM_000018.3(ACADVL):c.865G>A (p.Gly289Arg)]

NM_000018.3(ACADVL):c.865G>A (p.Gly289Arg)

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_000018.3(ACADVL):c.865G>A (p.Gly289Arg)
HGVS:
  • NC_000017.11:g.7222289G>A
  • NG_007975.1:g.7456G>A
  • NM_000018.3:c.865G>A
  • NP_000009.1:p.Gly289Arg
  • NC_000017.10:g.7125608G>A
  • NM_000018.2:c.865G>A
Protein change:
G289R
Links:
dbSNP: rs200788251
NCBI 1000 Genomes Browser:
rs200788251
Molecular consequence:
  • NM_000018.3:c.865G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000486424Counsylcriteria provided, single submitter
Likely pathogenic
(May 27, 2016)
unknownclinical testing

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

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

Citation Link,

SCV000820769Invitaecriteria provided, single submitter
Pathogenic
(Apr 2, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States.

Miller MJ, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ.

Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.

PubMed [citation]
PMID:
26385305
PMCID:
PMC4790081

Neuropsychological outcomes in fatty acid oxidation disorders: 85 cases detected by newborn screening.

Waisbren SE, Landau Y, Wilson J, Vockley J.

Dev Disabil Res Rev. 2013;17(3):260-8. doi: 10.1002/ddrr.1119.

PubMed [citation]
PMID:
23798014
PMCID:
PMC4137760
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000486424.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000820769.1

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

Description

This sequence change replaces glycine with arginine at codon 289 of the ACADVL protein (p.Gly289Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs200788251, ExAC 0.02%). This variant has been reported in combination with another ACADVL variant in individuals affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 27246109, 27209629, 14517516, 23480858). This variant is also known in the literature as Gly249Arg. ClinVar contains an entry for this variant (Variation ID: 370981). Experimental studies have shown that this missense change causes a large reduction in ACADVL enzyme activity (PMID: 23480858). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Mar 30, 2019

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