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

dbSNP: rs61755805

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001058357	SCV001222917	pathogenic	PRPH2-related disorder	2024-11-19	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). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PRPH2 protein function with a positive predictive value of 95%. 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
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815033	SCV005072370	pathogenic	Retinal dystrophy	2018-01-01	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