ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.820G>A (p.Gly274Ser)

gnomAD frequency: 0.00001  dbSNP: rs746368198
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000338902 SCV000329848 pathogenic not provided 2016-09-30 criteria provided, single submitter clinical testing The G274S variant has also previously been reported in association with SCAD deficiency (Pedersen et al., 2008). Functional analysis of G274S found that it is associated with reduced tetramer formation, increased aggregation tendency, and increased chaperone retention compared to wildtype similar to other pathogenic variants in the ACADS gene (Pedersen et al., 2008). Therefore, we interpret G274S to be a pathogenic variant.
Counsyl RCV000675088 SCV000800601 uncertain significance Deficiency of butyryl-CoA dehydrogenase 2017-09-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000675088 SCV000826273 uncertain significance Deficiency of butyryl-CoA dehydrogenase 2022-07-21 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 274 of the ACADS protein (p.Gly274Ser). This variant is present in population databases (rs746368198, gnomAD 0.005%). This missense change has been observed in individual(s) with short-chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 18523805). ClinVar contains an entry for this variant (Variation ID: 280061). 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 ACADS protein function. Experimental studies have shown that this missense change affects ACADS function (PMID: 18523805). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000675088 SCV002033252 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2021-11-07 criteria provided, single submitter clinical testing

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