Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001067304 | SCV001232358 | pathogenic | PRPH2-Related Disorders | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 220 of the PRPH2 protein (p.Arg220Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with PRPH2-related conditions (PMID: 32531846; Invitae). ClinVar contains an entry for this variant (Variation ID: 860907). 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%. 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, 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. |
NEI Ophthalmic Genomics Laboratory, |
RCV001250311 | SCV001424631 | likely pathogenic | Retinitis pigmentosa | 2020-01-07 | criteria provided, single submitter | clinical testing | The variant NM_000322.4:c.659G>C in the PRPH2 gene has not been reported to our knowledge . We found this variant in 2 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is not listed in dbSNP and/or HGMD. It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP3] and classified NM_000322.4:c.659G>C in the PRPH2 gene as a Likely Pathogenic mutation. |
NEI Ophthalmic Genomics Laboratory, |
RCV001250312 | SCV001424632 | likely pathogenic | Patterned dystrophy of the retinal pigment epithelium | 2020-01-07 | criteria provided, single submitter | clinical testing | The variant NM_000322.4:c.659G>C in the PRPH2 gene has not been reported to our knowledge . We found this variant in 2 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is not listed in dbSNP and/or HGMD. It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP3] and classified NM_000322.4:c.659G>C in the PRPH2 gene as a Likely Pathogenic mutation. |
Leiden Open Variation Database | RCV001530244 | SCV001744989 | likely pathogenic | not provided | 2021-04-06 | no assertion criteria provided | curation | Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters. |