NM_000018.4(ACADVL):c.1405C>T (p.Arg469Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Sep 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000756952.1

Allele description [Variation Report for NM_000018.4(ACADVL):c.1405C>T (p.Arg469Trp)]

NM_000018.4(ACADVL):c.1405C>T (p.Arg469Trp)

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.1405C>T (p.Arg469Trp)
HGVS:
  • NC_000017.11:g.7224040C>T
  • NG_007975.1:g.9207C>T
  • NM_000018.4:c.1405C>T
  • NM_001270448.1:c.1177C>T
  • NP_000009.1:p.Arg469Trp
  • NP_001257377.1:p.Arg393Trp
  • NC_000017.10:g.7127359C>T
  • NM_000018.2:c.1405C>T
  • NM_000018.3:c.1405C>T
  • P49748:p.Arg469Trp
Protein change:
R393W
Links:
UniProtKB: P49748#VAR_000362; dbSNP: rs113994170
NCBI 1000 Genomes Browser:
rs113994170
Molecular consequence:
  • NM_000018.3:c.1405C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000884950ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Sep 22, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000884950.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ACADVL c.1405C>T; p.Arg469Trp variant (rs113994170), also known as Arg429Trp, has been reported in multiple individuals with VLCAD deficiency, including three severely affected individuals that were homozygous for the variant (Andresen 1999). Additionally, functional studies have shown that the variant protein has significantly reduced enzymatic activity (Goetzman 2007, Hoffmann 2012). This variant is reported in ClinVar (Variation ID: 21017), and observed in the general population with low overall allele frequencies of 0.008 percent (1/13006 alleles, Exome Variant Server), and 0.003 percent (7/246250 alleles, Genome Aggregation Database). The arginine at codon 469 is well conserved across species, and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be damaging to the protein. Taken together, this variant is considered pathogenic. REFERENCES Andresen BS et al. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet. 1999 Feb;64(2):479-94. Goetzman ES et al. Expression and characterization of mutations in human very long-chain acyl-CoA dehydrogenase using a prokaryotic system. Mol Genet Metab. 2007 Jun;91(2):138-47. Hoffmann L et al. VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment. J Inherit Metab Dis. 2012 Mar;35(2):269-77.

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

Last Updated: Mar 30, 2019

Support Center