Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002983072 | SCV003294629 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 291 of the RPE65 protein (p.Ile291Val). This variant is present in population databases (rs199824408, gnomAD 0.05%). This missense change has been observed in individual(s) with RPE65-related conditions (PMID: 18722466; Invitae). 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 not expected to disrupt RPE65 protein function. 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. |