ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1837C>T (p.Arg613Trp) (rs118204014)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507731 SCV000602366 pathogenic not specified 2016-11-27 criteria provided, single submitter clinical testing
Counsyl RCV000001690 SCV000220191 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2014-03-29 criteria provided, single submitter literature only
GeneDx RCV000185733 SCV000238660 pathogenic not provided 2017-06-27 criteria provided, single submitter clinical testing The R613W missense mutation identified in the ACADVL gene has been reported previously in association with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Strauss et al., 1995). Functional studies have shown that the R613W mutation significantly impacts enzyme activity (Goetzman et al., 2007). The The variant is found in ACADVL panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000001690 SCV000914789 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2018-09-20 criteria provided, single submitter clinical testing The ACADVL c.1837C>T (p.Arg613Trp) variant has been reported in at least four studies and is found in a total of five probands with VLCAD deficiency including two in a homozygous state and three in a compound heterozygous state (Strauss et al. 1995; Gobin-Limballe et al. 2007; Laforet et al. 2009; Bouvier et al. 2017). Control data are unavailable for this variant, which is reported at a frequency of 0.00014 in the European (non-Finnish) population of the Exome Aggregation Consortium. Analysis of proband fibroblasts reported by revealed significantly lower VLCAD enzyme activity and no detectable ACADVL protein (Hale et al. 1985; Strauss et al. 1995; Aoyama et al. 1995). Souri et al. (1996) reported the p.Arg613Trp variant protein expressed in CHO cells had significantly less protein accumulation when compared to wild type despite normal mRNA levels, reduced VLCAD activity, and failure to homodimerize. Further, Goetzman et al. (2007) used a bacterial expression system to confirm that the p.Arg613Trp variant protein has no VLCAD activity. Based on the evidence, the p.Arg613Trp variant is classified as pathogenic for VLCAD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000001690 SCV000821526 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 613 of the ACADVL protein (p.Arg613Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs118204014, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another ACADVL variant in individuals affected with very long chain acyl-CoA dehydrogenase (PMID: 10077518, 7479827, 19327992, 17999356, 8554073). ClinVar contains an entry for this variant (Variation ID: 1623). Experimental studies have shown that this missense change abrogates ACADVL enzyme activity in vitro (PMID: 17374501, 8554073). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001690 SCV000021846 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 1996-01-01 no assertion criteria provided literature only

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