Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000211557 | SCV000268457 | uncertain significance | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2015-02-20 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000211557 | SCV002276727 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 372 of the ACADM protein (p.Ala372Asp). This variant is present in population databases (rs781424858, gnomAD 0.002%). This missense change has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 20434380, 27477829, 32778825). ClinVar contains an entry for this variant (Variation ID: 226073). 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 ACADM protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282048 | SCV002570495 | uncertain significance | not specified | 2022-07-05 | criteria provided, single submitter | clinical testing | Variant summary: ACADM c.1115C>A (p.Ala372Asp) results in a non-conservative amino acid change located in the acyl-CoA dehydrogenase/oxidase C-terminal domain (IPR009075) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251238 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1115C>A has been reported in the literature in at least one compound heterozygous individual affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency in whom the variant was confirmed to be in trans with a pathogenic variant (e.g. Smith_2010, Adhikari_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Two laboratories classified the variant as VUS and one classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Revvity Omics, |
RCV000211557 | SCV003825159 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2022-06-02 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000211557 | SCV001461477 | uncertain significance | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |