Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002038411 | SCV002312244 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 610 of the ETFDH protein (p.Gly610Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multiple Acyl-CoA dehydrogenase deficiency (PMID: 24522293, 35309592; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1519846). 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 ETFDH protein function with a positive predictive value of 80%. Studies have shown that this missense change alters ETFDH gene expression (PMID: 24522293). For these reasons, this variant has been classified as Pathogenic. |