NM_000018.3(ACADVL):c.1837C>T (p.Arg613Trp) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: May 11, 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:
RCV000001690.8

Allele description [Variation Report for NM_000018.3(ACADVL):c.1837C>T (p.Arg613Trp)]

NM_000018.3(ACADVL):c.1837C>T (p.Arg613Trp)

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.1837C>T (p.Arg613Trp)
Other names:
p.R613W:CGG>TGG
HGVS:
  • NC_000017.11:g.7224966C>T
  • NG_007975.1:g.10133C>T
  • NM_000018.3:c.1837C>T
  • NM_001033859.2:c.1771C>T
  • NM_001270448.1:c.1609C>T
  • NP_000009.1:p.Arg613Trp
  • NP_001029031.1:p.Arg591Trp
  • NP_001257377.1:p.Arg537Trp
  • NC_000017.10:g.7128285C>T
  • NM_000018.2:c.1837C>T
  • NM_001033859.1:c.1771C>T
  • P49748:p.Arg613Trp
Protein change:
R537W; ARG613TRP
Links:
UniProtKB: P49748#VAR_000365; OMIM: 609575.0003; dbSNP: rs118204014
NCBI 1000 Genomes Browser:
rs118204014
Molecular consequence:
  • NM_000018.3:c.1837C>T - 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
SCV000021846OMIMno assertion criteria providedPathogenic
(Jan 1, 1996)
germlineliterature only

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

SCV000220191Counsylcriteria provided, single submitter
Likely pathogenic
(Mar 29, 2014)
unknownliterature only

PubMed (7)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000821526Invitaecriteria provided, single submitter
Pathogenic
(May 11, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

Aoyama T, Souri M, Ushikubo S, Kamijo T, Yamaguchi S, Kelley RI, Rhead WJ, Uetake K, Tanaka K, Hashimoto T.

J Clin Invest. 1995 Jun;95(6):2465-73.

PubMed [citation]
PMID:
7769092
PMCID:
PMC295925

Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.

Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF.

Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10496-500.

PubMed [citation]
PMID:
7479827
PMCID:
PMC40638
See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000021846.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a patient with VLCAD deficiency (201475), Souri et al. (1996) identified compound heterozygosity for 2 mutations in the ACADVL gene: a 1837C-T transition, resulting in an arg613-to-trp (R613W) substitution, and a 135-bp deletion of nucleotides 343-477, resulting in the loss of 45 amino acids from the VLCAD protein (609575.0005).

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

From Counsyl, SCV000220191.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (7)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000821526.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine with tryptophan at codon 613 of the ACADVL protein (p.Arg613Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs118204014, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another ACADVL variant in individuals affected with very long chain acyl-CoA dehydrogenase (PMID: 10077518, 7479827, 19327992, 17999356, 8554073). ClinVar contains an entry for this variant (Variation ID: 1623). Experimental studies have shown that this missense change abrogates ACADVL enzyme activity in vitro (PMID: 17374501, 8554073). 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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