NM_000018.4(ACADVL):c.1097G>A (p.Arg366His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 25, 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:
RCV000185720.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.1097G>A (p.Arg366His)]

NM_000018.4(ACADVL):c.1097G>A (p.Arg366His)

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.1097G>A (p.Arg366His)
Other names:
p.R366H:CGT>CAT
HGVS:
  • NC_000017.11:g.7223152G>A
  • NG_007975.1:g.8319G>A
  • NM_000018.4:c.1097G>A
  • NM_001270448.1:c.869G>A
  • NP_000009.1:p.Arg366His
  • NP_001257377.1:p.Arg290His
  • NC_000017.10:g.7126471G>A
  • NM_000018.2:c.1097G>A
  • NM_000018.3:c.1097G>A
  • P49748:p.Arg366His
Protein change:
R290H
Links:
UniProtKB: P49748#VAR_000350; dbSNP: rs112406105
NCBI 1000 Genomes Browser:
rs112406105
Molecular consequence:
  • NM_000018.3:c.1097G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000238645GeneDxcriteria provided, single submitter
Pathogenic
(Jun 9, 2016)
germlineclinical testing

Citation Link,

SCV000860790EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Apr 25, 2018)
germlineclinical testing

Citation Link,

SCV000883344ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Dec 14, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000238645.12

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

Description

The R366H missense variant has been reported previously in association with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency in several unrelated individuals who were homozygous for R366H, or heterozygous for R366H and another pathogenic variant in the ACADVL gene (Antunes et al., 2013; Andresen et al., 1999; Gobin-Limballe et al., 2010; Evans et al., 2016). The R366H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R366C) and a nearby residue (Q368P) have been reported in the Human Gene Mutation Database in association with VLCAD deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore we interpret R366H to be a pathogenic variant.

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

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000860790.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000883344.1

#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: Apr 19, 2019

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