Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001329259 | SCV001520645 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-11-20 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001329259 | SCV002294099 | uncertain significance | Multiple acyl-CoA dehydrogenase deficiency | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 262 of the ETFDH protein (p.Leu262Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glutaric acidemia type II (PMID: 12359134). ClinVar contains an entry for this variant (Variation ID: 1028249). 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. Studies have shown that this missense change alters ETFDH gene expression (PMID: 12359134). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genomic Medicine Center of Excellence, |
RCV001329259 | SCV004810027 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2024-04-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690081 | SCV005185692 | uncertain significance | not specified | 2024-05-16 | criteria provided, single submitter | clinical testing | Variant summary: ETFDH c.786G>T (p.Leu262Phe) 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. The variant was absent in 251324 control chromosomes. c.786G>T has been reported in the literature in one individual affected with Glutaric Aciduria, Type 2c (Goodman_2002). These data indicate that 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 have been ascertained in the context of this evaluation (PMID: 12359134). ClinVar contains an entry for this variant (Variation ID: 1028249). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |