Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004527450 | SCV005038793 | likely pathogenic | RPE65-related recessive retinopathy | 2024-04-22 | reviewed by expert panel | curation | NM_000329.3(RPE65):c.1282_1303del (p.Gly428MetfsTer5) is a frameshift variant that introduces a premature stop codon into exon 12 of 14, and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who harbored the variant in the compound heterozygous state with the NM_000329.3(RPE65):c.1078G>C (p.Ala360Pro) variant confirmed in trans (PMID: 19431183). However, the proband was not counted for PM3 in order to avoid circularity. In summary, this variant meets the criteria to be classified as likely pathogenic for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: PVS1 and PM2_Supporting. (VCEP specifications version 1.0.0; date of approval 09/21/2023). |
| Labcorp Genetics |
RCV003052506 | SCV003353215 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2022-04-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gly428Metfs*5) in the RPE65 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPE65 are known to be pathogenic (PMID: 9326941, 9501220, 9843205, 18632300). 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. |