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NM_000018.4(ACADVL):c.1349G>A (p.Arg450His)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Aug 31, 2021)
Last evaluated:
Oct 1, 2020
Accession:
VCV000001634.8
Variation ID:
1634
Description:
single nucleotide variant
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NM_000018.4(ACADVL):c.1349G>A (p.Arg450His)

Allele ID
16673
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7223984 (GRCh38) GRCh38 UCSC
17: 7127303 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7127303G>A
NC_000017.11:g.7223984G>A
NG_007975.1:g.9151G>A
... more HGVS
Protein change
R450H, R374H, R428H, R473H
Other names
R410H
Canonical SPDI
NC_000017.11:7223983:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
OMIM: 609575.0014
dbSNP: rs118204016
ClinGen: CA251910
UniProtKB: P49748#VAR_000355
OMIM: 609575.0010
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Oct 1, 2020 RCV000001701.10
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Apr 23, 2018 RCV000724571.2
Pathogenic 1 no assertion criteria provided - RCV001003625.1
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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
884 960

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Apr 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000884952.1
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The ACADVL c.1349G>A; p.Arg450His variant (rs118204016), also known as Arg410His for traditional nomenclature, is reported multiple times in the literature in association with VLCAD deficiency … (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: SCV001364921.2
Submitted: (Jul 13, 2020)
Evidence details
Publications
PubMed (2)
Comment:
The NM_000018.3:c.1349G>A (NP_000009.1:p.Arg450His) [GRCH38: NC_000017.11:g.7223984G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported … (more)
Pathogenic
(Oct 01, 2020)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV000654930.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces arginine with histidine at codon 450 of the ACADVL protein (p.Arg450His). The arginine residue is highly conserved and there is a … (more)
Likely pathogenic
(Jan 27, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000225986.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (3)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Feb 01, 2001)
no assertion criteria provided
Method: literature only
VLCAD DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000021857.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001459255.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Jul 19, 2019)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001811368.1
Submitted: (Aug 31, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32581362, 31130284, … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
Abnormality of circulating enzyme level
Rhabdomyolysis
Allele origin: unknown
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV001162036.1
Submitted: (Sep 13, 2019)
Evidence details
Publications
PubMed (1)

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
Whole-genome sequencing of patients with rare diseases in a national health system. Turro E Nature 2020 PMID: 32581362
Clinical features and mutations in seven Chinese patients with very long chain acyl-CoA dehydrogenase deficiency. Zhang RN World journal of pediatrics : WJP 2014 PMID: 24801231
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
A new diagnostic test for VLCAD deficiency using immunohistochemistry. Ohashi Y Neurology 2004 PMID: 15210884
Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl. Fukao T Pediatric research 2001 PMID: 11158518
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
Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset. Smelt AH Annals of neurology 1998 PMID: 9546340
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL - - - -

Text-mined citations for rs118204016...

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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 07, 2021