Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001966130 | SCV002254330 | pathogenic | not provided | 2025-01-06 | 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 552 of the PDE6B protein (p.Arg552Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of autosomal recessive PDE6B-related conditions (internal data). 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: 1466663). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PDE6B protein function with a positive predictive value of 95%. This variant disrupts the p.Arg552 amino acid residue in PDE6B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8956055, 21655355, 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. |
| Institute of Human Genetics, |
RCV004816851 | SCV005072171 | likely pathogenic | Retinal dystrophy | 2020-01-01 | no assertion criteria provided | clinical testing |