ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.718G>T (p.Val240Phe)

dbSNP: rs192907397
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cytogenetics and Genomics Laboratory, Medical University of South Carolina RCV000754973 SCV000803383 likely pathogenic Leber congenital amaurosis 2018-06-01 criteria provided, single submitter research
Invitae RCV001244442 SCV001417662 likely pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 240 of the RPE65 protein (p.Val240Phe). This variant is present in population databases (rs192907397, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive RPE65-related conditions (PMID: 30870047; Invitae). 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: 559520). 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 with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003232070 SCV003929441 likely pathogenic Retinitis pigmentosa 20 2023-06-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000754973 SCV002092761 uncertain significance Leber congenital amaurosis 2020-07-22 no assertion criteria provided clinical testing

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