Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000579388 | SCV000787465 | likely pathogenic | Combined oxidative phosphorylation deficiency 34 | 2018-04-16 | criteria provided, single submitter | curation | This variant is interpreted as a Likely Pathogenic, for Combined oxidative phosphorylation deficiency 34, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect (PMID:25556185). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:25556185). |
| Baylor Genetics | RCV000579388 | SCV001522451 | uncertain significance | Combined oxidative phosphorylation deficiency 34 | 2020-07-09 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Invitae | RCV001860020 | SCV002290054 | uncertain significance | not provided | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 184 of the MRPS7 protein (p.Met184Val). This variant is present in population databases (rs115047866, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with congenital sensorineural deafness and significant hepatic and renal impairment (PMID: 25556185). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 489402). 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 MRPS7 protein function. Studies have shown that this missense change alters MRPS7 gene expression (PMID: 25556185). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252171 | SCV002523625 | likely pathogenic | See cases | 2020-04-02 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS3, PS4, PM2, PM3, PP1 |
| OMIM | RCV000579388 | SCV000681420 | pathogenic | Combined oxidative phosphorylation deficiency 34 | 2018-02-12 | no assertion criteria provided | literature only |