ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.646C>T (p.Pro216Ser)

dbSNP: rs61755805
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001058357 SCV001222917 pathogenic PRPH2-related disorder 2023-10-13 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 216 of the PRPH2 protein (p.Pro216Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 7754251, 8058286, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98695). 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.Pro216 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1684223, 12925772, 28076437). 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, National Institutes of Health RCV000787871 SCV001424708 likely pathogenic Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.646C>T in the PRPH2 gene has been previously studied(PMIDs 8058286, 7754251, 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 (rs61755805,CM941212). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PP1-M, PM1, PM2, PM5, PP3] and classified NM_000322.4:c.646C>T in the PRPH2 gene as a Likely Pathogenic mutation.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000085006 SCV001447663 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Retina International RCV000085006 SCV000117142 not provided not provided no assertion provided not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787871 SCV000926887 uncertain significance Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Leiden Open Variation Database RCV000085006 SCV001745170 likely pathogenic not provided 2021-05-21 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Julia Lopez, LOVD, Manon Peeters.
Clinical Genetics, Academic Medical Center RCV000085006 SCV001922868 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000085006 SCV001959886 likely pathogenic not provided no assertion criteria provided clinical testing

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