ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1532G>A (p.Arg511Gln) (rs200771970)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410771 SCV000487081 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2016-10-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000595069 SCV000700489 uncertain significance not provided 2016-12-05 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000410771 SCV001364935 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1532G>A (NP_000009.1:p.Arg511Gln) [GRCH38: NC_000017.11:g.7224243G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 21932095 . This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3
Invitae RCV000410771 SCV001592167 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 511 of the ACADVL protein (p.Arg511Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant also falls at the last nucleotide of exon 15 of the ACADVL coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs200771970, ExAC 0.02%). This variant has been observed in individual(s) with VLCAD deficiency (PMID: 21932095, 25652019, 2951924, 26385305, 26182500, 27209629). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 203587). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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