ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1700G>A (p.Arg567Gln) (rs398123084)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000259048 SCV000109738 uncertain significance not provided 2018-08-24 criteria provided, single submitter clinical testing
Invitae RCV000813614 SCV000953981 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 567 of the ACADVL protein (p.Arg567Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs398123084, ExAC 0.09%). This variant has been observed in combination with another ACADVL variant in individuals affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 23480858, Invitae). ClinVar contains an entry for this variant (Variation ID: 92278). Experimental studies have shown that this missense change abrogates ACADVL enzyme activity (PMID: 23480858). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV000813614 SCV001140233 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000813614 SCV001158615 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-03-21 criteria provided, single submitter clinical testing The ACADVL c.1700G>A; p.Arg567Gln variant (rs398123084) is reported in the literature in an individual with elevated acylcarnitine levels (Schiff 2013). In testing performed at ARUP Laboratories, this variant has also been observed in at least one individual with an abnormal newborn screen for VLCAD deficiency that also carried an additional pathogenic variant. The p.Arg567Gln variant is reported in ClinVar (Variation ID: 92278), and it is found in the general population with an overall allele frequency of 0.01% (23/210246 alleles) in the Genome Aggregation Database. The arginine at codon 567 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. In a biochemical VLCAD activity assay, the p.Arg567Gln variant protein exhibits 21% of wildtype activity (Schiff 2013). While this reduced activity may be attributable to reduced enzyme synthesis or stability by an uncertain mechanism, the decreased activity in the biochemical assay is consistent with reduced VLCAD activity measured in patient fibroblasts (Schiff 2013). Based on available information, the p.Arg567Gln variant is considered to be likely pathogenic. References: Schiff M et al. Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2013 May;109(1):21-7.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000259048 SCV001247040 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000813614 SCV001364939 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1700G>A (NP_000009.1:p.Arg567Gln) [GRCH38: NC_000017.11:g.7224663G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 23480858. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.