Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000211439 | SCV000268489 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2019-07-22 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000211439 | SCV000814260 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 397 of the ACADM protein (p.Tyr397Asn). This variant is present in population databases (rs759158371, gnomAD 0.05%). This missense change has been observed in individual(s) with MCAD deficiency (PMID: 18075239, 19064330, 21239873, 26947917). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1189A>T. ClinVar contains an entry for this variant (Variation ID: 226095). 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 not expected to disrupt ACADM protein function. Experimental studies have shown that this missense change affects ACADM function (PMID: 26947917). This variant disrupts the p.Tyr397 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been observed in individuals with ACADM-related conditions (PMID: 18075239, 19064330, 21239873, 26947917; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000211439 | SCV003928947 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-04-26 | criteria provided, single submitter | clinical testing | Variant summary: ACADM c.1189T>A (p.Tyr397Asn) results in a non-conservative amino acid change located in the Acyl-CoA dehydrogenase/oxidase C-terminal domain (IPR009075) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 250034 control chromosomes (gnomAD). c.1189T>A has been reported in the literature as a biallelic genotype in individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (e.g. Yokoi_2007, Woo_2011, Seo_2020, Li_2022). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, showing the variant had 0.9% residual activity when expressed in HEK293T cells (Hara_2016). The following publications have been ascertained in the context of this evaluation (PMID: 26947917, 36068006, 32901917, 21239873, 18075239). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000211439 | SCV004213199 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2024-03-09 | criteria provided, single submitter | clinical testing | |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000211439 | SCV004244581 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-12-20 | criteria provided, single submitter | clinical testing | PS3, PM3_Strong, PM2, PM1, PP3 |