Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000987489 | SCV001136789 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222651 | SCV002500644 | uncertain significance | not specified | 2022-03-25 | criteria provided, single submitter | clinical testing | Variant summary: ETFDH c.1106G>C (p.Gly369Ala) 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 251410 control chromosomes. c.1106G>C has been reported in the literature as a homozygous genotype in at-least one in individual affected with Glutaric Aciduria, Type 2c (Multiple acyl-CoA dehydrogenase deficiency) (example, van Rijt_2020 citing Gautschi_2015). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Invitae | RCV000987489 | SCV003208587 | uncertain significance | Multiple acyl-CoA dehydrogenase deficiency | 2022-06-15 | criteria provided, single submitter | clinical testing | 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. 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: 802102). This variant has not been reported in the literature in individuals affected with ETFDH-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 369 of the ETFDH protein (p.Gly369Ala). |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000987489 | SCV003806818 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2022-05-16 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 supporting, PM2 moderated, PM3 supporting, PP3 supporting, PP4 |