Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001923409 | SCV002188013 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2022-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 244 of the RPE65 protein (p.Gly244Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPE65-related conditions. 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 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. |
| 3billion | RCV005253935 | SCV005905756 | uncertain significance | Retinitis pigmentosa 20 | 2023-07-13 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.97). A different missense change at the same codon (p.Gly244Val) has been reported to be associated with RPE65 related disorder (PMID: 18722466). However the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. |