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

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 21, 2020
Accession:
VCV000203580.9
Variation ID:
203580
Description:
single nucleotide variant
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NM_000018.4(ACADVL):c.1097G>A (p.Arg366His)

Allele ID
200333
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7223152 (GRCh38) GRCh38 UCSC
17: 7126471 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P49748:p.Arg366His
NC_000017.10:g.7126471G>A
NC_000017.11:g.7223152G>A
... more HGVS
Protein change
R366H, R290H, R344H, R389H
Other names
p.R366H:CGT>CAT
Canonical SPDI
NC_000017.11:7223151:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Links
ClinGen: CA312265
UniProtKB: P49748#VAR_000350
dbSNP: rs112406105
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Apr 25, 2018 RCV000185720.3
Pathogenic/Likely pathogenic 7 criteria provided, multiple submitters, no conflicts Sep 21, 2020 RCV000411732.8
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ACADVL - - GRCh38
GRCh37
889 970

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 27, 2016)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: unknown
Counsyl
Accession: SCV000486429.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Pathogenic
(Jun 09, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000238645.12
Submitted: (Jan 29, 2019)
Evidence details
Comment:
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 … (more)
Pathogenic
(Apr 25, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000860790.1
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Jan 09, 2019)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915777.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (6)
Comment:
The ACADVL c.1097G>A (p.Arg366His) missense variant has been reported in at least four studies in which it is identified in at least seven individuals with … (more)
Pathogenic
(Nov 01, 2019)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001364915.2
Submitted: (Jul 13, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The NM_000018.3:c.1097G>A (NP_000009.1:p.Arg366His) [GRCH38: NC_000017.11:g.7223152G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported … (more)
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF
Allele origin: germline
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001443688.1
Submitted: (Jul 31, 2020)
Evidence details
Comment:
This variant has been observed as homozygous or compound heterozygous change in several individuals affected with very long chain acyl-CoA dehydrogenase (VLCAD)(PMID: 9973285, 20060901, 24263034, … (more)
Pathogenic
(Mar 28, 2020)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000883344.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The ACADVL c.1097G>A; p.Arg366His variant (rs112406105), also known as Arg326His, has been reported in individuals with VLCAD deficiency both in the homozygous state and as … (more)
Pathogenic
(Sep 21, 2020)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV000836322.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces arginine with histidine at codon 366 of the ACADVL protein (p.Arg366His). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001455139.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria. Evans M Molecular genetics and metabolism 2016 PMID: 27246109
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 Molecular genetics and metabolism 2015 PMID: 26385305
Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening. Brown A Molecular genetics and metabolism 2014 PMID: 25456746
Intermittent rhabdomyolysis with adult onset associated with a mutation in the ACADVL gene. Antunes AP Journal of clinical neuromuscular disease 2013 PMID: 24263034
VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment. Hoffmann L Journal of inherited metabolic disease 2012 PMID: 21932095
Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches. Gobin-Limballe S Biochimica et biophysica acta 2010 PMID: 20060901
VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis. Boneh A Molecular genetics and metabolism 2006 PMID: 16488171
Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Andresen BS American journal of human genetics 1999 PMID: 9973285
Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene. Andresen BS Human molecular genetics 1996 PMID: 8845838
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL - - - -

Text-mined citations for rs112406105...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 26, 2021