ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1406G>A (p.Arg469Gln) (rs398123083)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169627 SCV000221156 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2015-02-25 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790745 SCV000225985 pathogenic not provided 2012-08-06 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000169627 SCV001364931 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1406G>A (NP_000009.1:p.Arg469Gln) [GRCH38: NC_000017.11:g.7224041G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 9973285. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3
Invitae RCV000169627 SCV001413446 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 469 of the ACADVL protein (p.Arg469Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in an individual affected with very long chain acyl-CoA dehydrogenase deficiency (PMID: 25834949). ClinVar contains an entry for this variant (Variation ID: 92276). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Arg469 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9973285, 17999356, 27246109, 17374501). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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