Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001075618 | SCV001241245 | likely pathogenic | Retinal dystrophy | 2019-02-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001346727 | SCV001540952 | pathogenic | PRPH2-Related Disorders | 2022-12-14 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg220 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9443872, 16916875, 17653047; 29555955.). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRPH2 function (PMID: 26796962). 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 PRPH2 protein function. ClinVar contains an entry for this variant (Variation ID: 98699). This missense change has been observed in individuals with PRPH2-related conditions (PMID: 8994365, 30822235). This variant is present in population databases (rs61755810, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 220 of the PRPH2 protein (p.Arg220Gln). |
Gene |
RCV000085011 | SCV001765310 | likely pathogenic | not provided | 2023-04-12 | criteria provided, single submitter | clinical testing | Identified in patients with vitelliform macular dystrophy and pattern dystrophy in published literature (Keen and Inglehearn, 1996; George Priya Doss et al., 2014); Observed in homozygous state in a patient in published literature (Kahn et al., 2019) with pediatric-onset cone-rod dystrophy and not observed in homozygous state in controls. Heterozygous parents had macular abnormalities.; In vitro functional studies demonstrate enhanced splicing and increased protein expression in murine retinas, which may affect cone degeneration (Becirovic et al., 2016); 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: 34411390, 34240658, 24629188, 8956033, 8675410, 30822235, 31456290, 26796962, 8994365, 36393903, 36648066) |
Retina International | RCV000085011 | SCV000117147 | not provided | not provided | no assertion provided | not provided | ||
Sharon lab, |
RCV001003141 | SCV001161210 | likely pathogenic | Retinitis pigmentosa | 2019-06-23 | no assertion criteria provided | research | |
Leiden Open Variation Database | RCV000085011 | SCV001744990 | pathogenic | not provided | 2021-04-06 | no assertion criteria provided | curation | Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Global Variome, with Curator vacancy, LOVD, Manon Peeters. |