Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001075367 | SCV001240988 | likely pathogenic | Retinal dystrophy | 2018-06-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001213611 | SCV001385248 | pathogenic | PRPH2-Related Disorders | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 179 of the PRPH2 protein (p.Trp179Cys). This variant is present in population databases (rs779414078, gnomAD 0.004%). This missense change has been observed in individuals with retinitis pigmentosa (PMID: 32037395, 32531846; Invitae). ClinVar contains an entry for this variant (Variation ID: 866955). 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. This variant disrupts the p.Trp179 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10862101). 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. |
NEI Ophthalmic Genomics Laboratory, |
RCV001250371 | SCV001424704 | likely pathogenic | Patterned dystrophy of the retinal pigment epithelium | 2020-01-07 | criteria provided, single submitter | clinical testing | The variant NM_000322.4:c.537G>T in the PRPH2 gene has not been reported to our knowledge . 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 (rs779414078). It is present in gnomAD browser (AF 0.00000406). This variant is not already listed in ClinVar. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP3] and classified NM_000322.4:c.537G>T in the PRPH2 gene as a Likely Pathogenic mutation. |
Gene |
RCV001530303 | SCV001819862 | likely pathogenic | not provided | 2021-06-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 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: 27535533, 32531846) |
Leiden Open Variation Database | RCV001530303 | SCV001745071 | likely pathogenic | not provided | 2021-04-06 | no assertion criteria provided | curation | Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters. |