Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000438661 | SCV000524231 | likely pathogenic | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | The G167S variant in the PRPH2 gene has been reported previously in association with PRPH2-related retinal dystrophies (Testa et al., 2005; Jin et al., 2008; Zaneveld et al., 2015). The G167S variant is not observed in large population cohorts (Lek et al., 2016). The G167S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in the same codon (G167D) and in nearby residues (C165R/Y, D170S, R172W/G/Q) have been reported in the Human Gene Mutation Database in association with PRPH2-related retinal dystrophies (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret G167S as a likely pathogenic variant. |
Invitae | RCV001055454 | SCV001219847 | pathogenic | PRPH2-Related Disorders | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 167 of the PRPH2 protein (p.Gly167Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant pattern dystrophy or retinitis pigmentosa (PMID: 16024869, 23591405, 25324289, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 143070). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001073378 | SCV001238919 | pathogenic | Retinal dystrophy | 2019-01-04 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000438661 | SCV001246206 | pathogenic | not provided | 2019-02-01 | criteria provided, single submitter | clinical testing | |
NEI Ophthalmic Genomics Laboratory, |
RCV001250331 | SCV001424651 | likely pathogenic | Stargardt disease | 2020-01-07 | criteria provided, single submitter | clinical testing | The variant NM_000322.4:c.499G>A in the PRPH2 gene has been previously studied(PMIDs 16024869, 22863181, 23591405, 25324289, 25474345, 28559085). We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs527236098,CM052911). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP1, PP3, PP5] and classified NM_000322.4:c.499G>A in the PRPH2 gene as a Likely Pathogenic mutation. |
Institute of Medical Genetics and Applied Genomics, |
RCV000438661 | SCV001448002 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000438661 | SCV004026291 | pathogenic | not provided | 2023-02-28 | criteria provided, single submitter | clinical testing | PM1, PP3, PM5, PP4, PS4, PM2_SUP |
Dept Of Ophthalmology, |
RCV001073378 | SCV004707353 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
Department of Ophthalmology and Visual Sciences Kyoto University | RCV000132579 | SCV000172522 | pathogenic | Retinitis pigmentosa | no assertion criteria provided | not provided | Converted during submission to Pathogenic. | |
Leiden Open Variation Database | RCV000438661 | SCV001744954 | pathogenic | not provided | 2021-06-19 | no assertion criteria provided | curation | Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters, Yoshito Koyanagi. |