Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001935533 | SCV002189331 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-08-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1416115). This missense change has been observed in individual(s) with multiple acyl-CoA dehydrogenase deficiency (PMID: 30022752). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 331 of the ETFDH protein (p.Asn331Ile). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323953 | SCV004028883 | uncertain significance | not specified | 2023-07-27 | criteria provided, single submitter | clinical testing | Variant summary: ETFDH c.992A>T (p.Asn331Ile) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. This alters a highly conserved residue in which another missense change has been found in association with disease (HGMD). The variant was absent in 251360 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.992A>T has been reported in the literature in an individual affected with Multiple acyl-CoA dehydrogenase deficiency who was compound heterozygous with a pathogenic variant (Gao_2018). These data suggest the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 30022752). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Fulgent Genetics, |
RCV001935533 | SCV005664659 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2024-04-18 | criteria provided, single submitter | clinical testing |