Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000622603 | SCV000742451 | pathogenic | Inborn genetic diseases | 2017-05-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002513217 | SCV003441188 | pathogenic | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 352 of the FOXRED1 protein (p.Arg352Trp). This variant is present in population databases (rs387907087, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of mitochondrial complex I deficiency (PMID: 20858599, 33613441). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 31048). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FOXRED1 protein function. Studies have shown that this missense change alters FOXRED1 gene expression (PMID: 20858599). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000024042 | SCV000045333 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 19 | 2010-12-15 | no assertion criteria provided | literature only |