ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.647C>T (p.Pro216Leu)

gnomAD frequency: 0.00001  dbSNP: rs61755806
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085007 SCV000517301 pathogenic not provided 2015-05-20 criteria provided, single submitter clinical testing The P216L variant in the PRPH2 gene has been reported previously in association with autosomal dominantretinitis pigmentosa (Loewen et al., 2003; Kajiwara et al., 1991). The P216L variant was not observed inapproximately 6,500 samples from individuals of European and African American ancestry in the NHLBI ESPExome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret P216L as a pathogenic variant.
Invitae RCV001063368 SCV001228209 pathogenic PRPH2-related disorder 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 216 of the PRPH2 protein (p.Pro216Leu). This variant is present in population databases (rs61755806, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 1684223, 28076437). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13164). 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%. Experimental studies have shown that this missense change affects PRPH2 function (PMID: 12925772). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075781 SCV001241414 pathogenic Retinal dystrophy 2019-07-03 criteria provided, single submitter clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001003142 SCV001424709 pathogenic Retinitis pigmentosa 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.647C>T in the PRPH2 gene has been previously studied(PMIDs 1684223, 12925772, 28559085). We found this variant in 3 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs61755806,CM910324). It is present in gnomAD browser (AF 0.00000406). It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PP1-M, PM1, PM2, PM3, PM5, PP3, PP5] and classified NM_000322.4:c.647C>T in the PRPH2 gene as a Pathogenic mutation.
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250376 SCV001424711 pathogenic Patterned dystrophy of the retinal pigment epithelium 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.647C>T in the PRPH2 gene has been previously studied(PMIDs 1684223, 12925772, 28559085). We found this variant in 3 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs61755806,CM910324). It is present in gnomAD browser (AF 0.00000406). It is enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PS4, PP1-M, PM1, PM2, PM3, PM5, PP3, PP5] and classified NM_000322.4:c.647C>T in the PRPH2 gene as a Pathogenic mutation.
Dept Of Ophthalmology, Nagoya University RCV001075781 SCV004707337 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
OMIM RCV000014050 SCV000034297 pathogenic Retinitis pigmentosa 7 1991-12-12 no assertion criteria provided literature only
Retina International RCV000085007 SCV000117143 not provided not provided no assertion provided not provided
Sharon lab, Hadassah-Hebrew University Medical Center RCV001003142 SCV001161211 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research
Leiden Open Variation Database RCV000085007 SCV001745173 uncertain significance not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Global Variome, with Curator vacancy, Julia Lopez, LOVD, Manon Peeters.

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