Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001378635 | SCV001576250 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 337 of the ACADM protein (p.Tyr337Ser). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 16763904, 23028790, 34539730). This variant is also known as Y312S. ClinVar contains an entry for this variant (Variation ID: 1067387). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ACADM function (PMID: 24966162). For these reasons, this variant has been classified as Pathogenic. |
| Beijing Key Laboratry for Genetics of Birth Defects, |
RCV001378635 | SCV001739491 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2020-02-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001378635 | SCV004039019 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-08-02 | criteria provided, single submitter | clinical testing | Variant summary: ACADM c.1010A>C (p.Tyr337Ser) results in a non-conservative amino acid change located in the C-terminal domain (IPR009075) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251418 control chromosomes (gnomAD). c.1010A>C has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (e.g. Sturm_2012, Rhead_2006, Liu_2021) . These data indicate that the variant is very likely to be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated that the variant results in ~8.5% of normal activity in both homozygous patients derived cells, and in an in vitro expression system (Koster_2014, Sturm_2012). The following publications have been ascertained in the context of this evaluation (PMID: 23028790, 16763904, 34539730, 24966162). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001378635 | SCV004217189 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2023-04-16 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001378635 | SCV002092863 | likely pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2019-06-26 | no assertion criteria provided | clinical testing |