ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.164C>T (p.Pro55Leu)

gnomAD frequency: 0.00001  dbSNP: rs147442301
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000023585 SCV000793186 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2017-07-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000023585 SCV000914564 pathogenic Deficiency of butyryl-CoA dehydrogenase 2018-08-14 criteria provided, single submitter clinical testing The ACADS c.164C>T (p.Pro55Leu) missense variant has been reported in four studies in which it is found in a total of six individuals with SCAD deficiency, including in one with the variant in a homozygous state and in five in a compound heterozygous state. All individuals carrying the variant were diagnosed with SCAD deficiency through newborn screening and were clinically asymptomatic, even during follow-up in childhood (Jethva and Ficicioqlu 2008; Shirao et al. 2010; An et al. 2016; Kim et al. 2016). In addition, Huang et al. (2016) reported the p.Pro55Leu variant in approximately 20% of 17 clinically asymptomatic Chinese children who were identified through newborn screening as having SCAD deficiency. Control data are unavailable for this variant, which is reported at a frequency of 0.00092 in the East Asian population of the Exome Aggregation Consortium. Shirao et al. (2010) performed in vitro testing of the variant and found that HEK293 cells that were transfected with the variant protein had 6.67% enzymatic activity compared to wild type. When the variant was co-transfected with wild type protein, 60-70% of normal enzymatic activity was observed. Based on the collective evidence, the p.Pro55Leu variant is classified as pathogenic for SCAD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genome-Nilou Lab RCV000023585 SCV002033277 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2021-11-07 criteria provided, single submitter clinical testing
Invitae RCV000023585 SCV002243243 pathogenic Deficiency of butyryl-CoA dehydrogenase 2021-10-14 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 55 of the ACADS protein (p.Pro55Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs147442301, ExAC 0.09%). This missense change has been observed in individuals with short chain acyl-CoA dehydrogenase deficiency (PMID: 18951053, 20376488, 27938594, 28018444). ClinVar contains an entry for this variant (Variation ID: 30611). 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: 20376488). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000023585 SCV000044876 pathogenic Deficiency of butyryl-CoA dehydrogenase 2010-06-01 no assertion criteria provided literature only
PerkinElmer Genomics RCV000023585 SCV002021040 pathogenic Deficiency of butyryl-CoA dehydrogenase 2020-08-06 no assertion criteria provided clinical testing

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