Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000634896 | SCV000756264 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 483 of the ETFDH protein (p.Pro483Leu). This variant is present in population databases (rs377656387, gnomAD 0.004%). This missense change has been observed in individual(s) with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (PMID: 17412732, 17584774, 24190796; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31602). 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 ETFDH protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ETFDH function (PMID: 17584774, 22611163). For these reasons, this variant has been classified as Pathogenic. |
Centogene AG - |
RCV001250164 | SCV001424408 | pathogenic | Acyl-CoA dehydrogenase deficiency, glutaric acidemia type II | criteria provided, single submitter | clinical testing | ||
Ce |
RCV002054473 | SCV002497295 | likely pathogenic | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | ETFDH: PM3:Strong, PM2, PS3:Supporting |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000634896 | SCV002583715 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2022-09-22 | criteria provided, single submitter | clinical testing | PS3 PM3 PM2 PM1 PP3 |
Revvity Omics, |
RCV000634896 | SCV003821405 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2022-10-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000634896 | SCV004194785 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-09-27 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000024306 | SCV000045597 | pathogenic | Glutaric acidemia iic, late-onset | 2007-08-01 | no assertion criteria provided | literature only | |
Natera, |
RCV001831606 | SCV002084873 | pathogenic | Glutaric acidemia type 2C | 2020-12-14 | no assertion criteria provided | clinical testing |