Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384458 | SCV001583959 | pathogenic | not provided | 2024-05-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 23 of the RHO protein (p.Pro23Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant inherited retinal dystrophy (PMID: 1833777; Invitae). ClinVar contains an entry for this variant (Variation ID: 1071889). 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 RHO protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects RHO function (PMID: 8253795, 19913029, 24106275, 30977563). This variant disrupts the p.Pro23 amino acid residue in RHO. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2137202, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001384458 | SCV003840834 | pathogenic | not provided | 2022-09-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate increased misfolding, decreased expression, and a damaging effect on transducin activation (Krebs et al., 2010; Opefi et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 1833777, 10668933, 35472194, 30977563, 19913029, 21094163, 8253795, 24106275, 27654411, 27149983) |
| Dept Of Ophthalmology, |
RCV003888084 | SCV004705636 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
| Institute of Human Genetics, |
RCV003888084 | SCV005071938 | pathogenic | Retinal dystrophy | 2008-01-01 | criteria provided, single submitter | clinical testing |