Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratoire de Génétique Moléculaire Institut de Recherche Necker Enfants Malades, |
RCV001002680 | SCV001160697 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV003769390 | SCV004629481 | likely pathogenic | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with autosomal recessive combined oxidative phosphorylation deficiency (PMID: 31680380; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 83 of the GFM1 protein (p.Asp83Val). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 812090). 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 GFM1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702570 | SCV005203070 | uncertain significance | not specified | 2024-07-09 | criteria provided, single submitter | clinical testing | Variant summary: GFM1 c.248A>T (p.Asp83Val) results in a non-conservative amino acid change located in the Translational (tr)-type GTP-binding domain (IPR000795) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251474 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.248A>T has been reported in the literature in at-least one individual affected with Combined Oxidative Phosphorylation Deficiency 1 (example: Barcia_2020) . These data do not allow any conclusion about variant significance. 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: 31680380). ClinVar contains an entry for this variant (Variation ID: 812090). Based on the evidence outlined above, the variant was classified as uncertain significance. |