Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001565464 | SCV001788812 | pathogenic | not provided | 2020-06-10 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with abnormal localization of the mutant P493S PRPF3 protein in photoreceptor cells (Comitato et al., 2007); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 33576794, 32036094, 16799052, 21378395, 17517693, 27302685, 23647439, 11773002) |
Labcorp Genetics |
RCV001565464 | SCV003523506 | pathogenic | not provided | 2024-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 493 of the PRPF3 protein (p.Pro493Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with retinitis pigmentosa (PMID: 11773002, 16799052, 21378395, 33576794). ClinVar contains an entry for this variant (Variation ID: 3353). 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 expected to disrupt PRPF3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PRPF3 function (PMID: 17517693). For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV004814816 | SCV005068660 | pathogenic | Retinal dystrophy | 2021-01-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000003517 | SCV000023675 | pathogenic | Retinitis pigmentosa 18 | 2002-01-01 | no assertion criteria provided | literature only |