Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001304649 | SCV001493941 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with glycine at codon 452 of the RPE65 protein (p.Val452Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 9501220). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 13116). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
| Gene |
RCV000085169 | SCV001827970 | likely pathogenic | not provided | 2020-09-09 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9501220) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114190 | SCV003800726 | uncertain significance | not specified | 2023-01-05 | criteria provided, single submitter | clinical testing | Variant summary: RPE65 c.1355T>G (p.Val452Gly) results in a non-conservative amino acid change to a highly conserved residue in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250734 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1355T>G has been reported in the literature in an individual affected with retinitis pigmentosa (Morimura_1998). The individual was reported as compound heterozygous with another known pathogenic missense variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS. |
| OMIM | RCV000013995 | SCV000034242 | pathogenic | Retinitis pigmentosa 20 | 1998-03-17 | no assertion criteria provided | literature only | |
| Retina International | RCV000085169 | SCV000117306 | not provided | not provided | no assertion provided | not provided |