ClinVar Miner

Submissions for variant NM_014384.3(ACAD8):c.409G>A (p.Gly137Arg)

gnomAD frequency: 0.00004  dbSNP: rs371449613
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000535761 SCV000645959 pathogenic Deficiency of isobutyryl-CoA dehydrogenase 2023-07-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects ACAD8 function (PMID: 16857760). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACAD8 protein function. ClinVar contains an entry for this variant (Variation ID: 468863). This missense change has been observed in individual(s) with isobutyryl-CoA dehydrogenase deficiency (PMID: 16857760, 35154245). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs371449613, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 137 of the ACAD8 protein (p.Gly137Arg).
CeGaT Center for Human Genetics Tuebingen RCV000994754 SCV001148496 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000535761 SCV003822428 uncertain significance Deficiency of isobutyryl-CoA dehydrogenase 2020-09-22 criteria provided, single submitter clinical testing
GeneDx RCV000994754 SCV004168011 uncertain significance not provided 2023-10-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 24635911, 34426522, 16857760, 35154245)

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