Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001383022 | SCV001582030 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn356Metfs*17) 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). 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 premature translational stop signal has been observed in individual(s) with autosomal recessive Leber congenital amaurosis (PMID: 9326927). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98821). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000013992 | SCV001737349 | pathogenic | Leber congenital amaurosis 2 | 2021-06-10 | criteria provided, single submitter | clinical testing | |
Genetics and Molecular Pathology, |
RCV002466426 | SCV002761671 | pathogenic | RPE65-related recessive retinopathy | 2022-01-14 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000013992 | SCV000034239 | pathogenic | Leber congenital amaurosis 2 | 1997-10-01 | no assertion criteria provided | literature only | |
Retina International | RCV000085145 | SCV000117282 | not provided | not provided | no assertion provided | not provided | ||
Laboratory of Genetics in Ophthalmology, |
RCV000013992 | SCV001425581 | pathogenic | Leber congenital amaurosis 2 | no assertion criteria provided | research | ||
Natera, |
RCV001826772 | SCV002092747 | pathogenic | Leber congenital amaurosis | 2021-03-08 | no assertion criteria provided | clinical testing |