Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414551 | SCV000491193 | likely pathogenic | not provided | 2016-08-17 | criteria provided, single submitter | clinical testing | The R136W variant in the FOXRED1 gene has been reported previously in the compound heterozygous state, along with a frameshift variant, in one patient with mitochondrial complex I deficiency (Haack et al., 2012). The R136W variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R136W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R136W as a likely pathogenic variant. |
| Institute of Human Genetics Munich, |
RCV000578347 | SCV000680238 | pathogenic | Mitochondrial complex I deficiency | 2017-11-15 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV002288985 | SCV002579135 | likely pathogenic | Mitochondrial complex 1 deficiency, nuclear type 19 | 2022-04-20 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV002288985 | SCV004047430 | likely pathogenic | Mitochondrial complex 1 deficiency, nuclear type 19 | criteria provided, single submitter | clinical testing | The missense variant c.406C>T (p.Arg136Trp) in FOXRED1 gene has been reported previously in the compound heterozygous state, along with a frameshift variant, in one patient with mitochondrial complex I deficiency (Haack et al., 2012). This variant has been reported to the ClinVar database as Pathogenic. The p.Arg136Trp variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.002388% is reported in gnomAD. The amino acid Arg at position 136 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Arg136Trp in FOXRED1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. |