Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000689657 | SCV000817320 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2024-03-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln4Argfs*27) 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 present in population databases (rs747393487, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RPE65-related conditions. ClinVar contains an entry for this variant (Variation ID: 569113). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003465570 | SCV004209252 | likely pathogenic | Leber congenital amaurosis 2 | 2024-02-24 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV005253067 | SCV005906341 | pathogenic | Retinitis pigmentosa 20 | 2023-12-03 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with RPE65 related disorder (ClinVar ID: VCV000569113 /PMID: 31429209). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |