Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 2, 2020
Accession:
VCV000166647.9
Variation ID:
166647
Description:
single nucleotide variant
Help

NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)

Allele ID
177030
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7224379 (GRCh38) GRCh38 UCSC
17: 7127698 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7127698C>T
NC_000017.11:g.7224379C>T
NG_007975.1:g.9546C>T
... more HGVS
Protein change
R531W, R455W, R509W, R554W
Other names
-
Canonical SPDI
NC_000017.11:7224378:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00033
Trans-Omics for Precision Medicine (TOPMed) 0.00039
The Genome Aggregation Database (gnomAD), exomes 0.00044
Exome Aggregation Consortium (ExAC) 0.00048
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00038
The Genome Aggregation Database (gnomAD) 0.00039
Links
ClinGen: CA233436
dbSNP: rs146379816
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Nov 3, 2017 RCV000185729.4
Uncertain significance 1 criteria provided, single submitter Nov 16, 2015 RCV000208321.1
Uncertain significance 1 criteria provided, single submitter Mar 11, 2019 RCV001192883.1
Conflicting interpretations of pathogenicity 6 criteria provided, conflicting interpretations Nov 2, 2020 RCV000652029.8
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ACADVL - - GRCh38
GRCh37
898 981

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 16, 2015)
criteria provided, single submitter
Method: clinical testing
Primary dilated cardiomyopathy
Allele origin: germline
Blueprint Genetics
Accession: SCV000263752.2
Submitted: (Jan 15, 2016)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Nov 25, 2013)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000202128.7
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Jun 05, 2017)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: unknown
Counsyl
Accession: SCV000791958.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (3)
Uncertain significance
(Nov 03, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884951.1
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The ACADVL c.1591C>T; p.Arg531Trp variant (also known as Arg491Trp) is published in the medical literature in at least two individuals with suspected very long-chain acyl-CoA … (more)
Uncertain significance
(Aug 09, 2018)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000914788.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (3)
Comment:
The ACADVL c.1591C>T (p.Arg531Trp) variant is a missense variant that has been reported in a compound heterozygous state with a canonical splice site variant in … (more)
Likely pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Baylor Genetics
Accession: SCV001163426.1
Submitted: (Sep 27, 2019)
Evidence details
Uncertain significance
(Mar 11, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361315.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: ACADVL c.1591C>T (p.Arg531Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Likely 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: SCV001365228.2
Submitted: (Jul 13, 2020)
Evidence details
Publications
PubMed (2)
Comment:
The NM_000018.3:c.1591C>T (NP_000009.1:p.Arg531Trp) [GRCH38: NC_000017.11:g.7224379C>T] variant in ACADVL gene is interpretated to be Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been … (more)
Likely pathogenic
(Nov 02, 2020)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV000773889.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces arginine with tryptophan at codon 531 of the ACADVL protein (p.Arg531Trp). The arginine residue is moderately conserved and there is a … (more)
Uncertain significance
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Natera, Inc.
Accession: SCV001459259.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

Help
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

Help
Title Author Journal Year Link
Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency. Rovelli V Molecular genetics and metabolism 2019 PMID: 31031081
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
Diagnosing childhood-onset inborn errors of metabolism by next-generation sequencing. Ghosh A Archives of disease in childhood 2017 PMID: 28468868
Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database. Pena LD Molecular genetics and metabolism 2016 PMID: 27209629
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
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. Tabor HK American journal of human genetics 2014 PMID: 25087612
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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL - - - -

Text-mined citations for rs146379816...

Help
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 Dec 04, 2021