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To address the molecular etiology of retinal degeneration, specifically the\n                    <jats:italic>PRPH2<\/jats:italic>\n                    \u2010related retinopathies, we reviewed genotype and phenotype information obtained from 187 eyeGENE\u00ae participants from 161 families. Clinical details were provided by referring clinicians participating in the eyeGENE\u00ae Network. The cohort was sequenced for variants in\n                    <jats:italic>PRPH2<\/jats:italic>\n                    . Variant complementary DNA clusters and cohort frequency were compared to variants in public databases to help us to determine pathogenicity by current American College of Medical Genetics and Genomics\/Association for Molecular Pathology interpretation criteria. The most frequent variant was c.828+3A&gt;T, which affected 28 families (17.4%), and 25 of 79 (31.64%) variants were novel. The majority of missense variants clustered in the D2 intracellular loop of the peripherin\u20102 protein, constituting a hotspot. Disease enrichment was noted for 23 (29.1%) of the variants. Hotspot and disease\u2010enrichment evidence modified variant classification for 16.5% of variants. The missense allele p.Arg172Trp was associated with a younger age of onset. To the best of our knowledge, this is the largest patient cohort review of\n                    <jats:italic>PRPH2<\/jats:italic>\n                    \u2010related retinopathy. Large disease gene\u2010specific cohorts permit gene modeling for hotspot and disease\u2010enrichment analysis, providing novel variant classification evidence, including for novel missense variants.\n                  <\/jats:p>","DOI":"10.1002\/humu.24065","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T18:12:57Z","timestamp":1591985577000},"page":"1528-1539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genotype\u2013phenotype associations in a large\n                    <i>PRPH2<\/i>\n                    \u2010related retinopathy cohort"],"prefix":"10.1155","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2022-4282","authenticated-orcid":false,"given":"Melissa J.","family":"Reeves","sequence":"first","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry E.","family":"Goetz","sequence":"additional","affiliation":[{"name":"Office of the Director National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guan","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Blain","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih M.","family":"Zein","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santa J.","family":"Tumminia","sequence":"additional","affiliation":[{"name":"Office of the Director National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute\/National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000000052"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22096-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12193"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.01.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.3.424"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-1399-9_5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq410"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.154906"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0295-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-251397"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi901622w"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu014"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-74904-4_23"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh211"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048414i"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6549"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-16343"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2018-313278"},{"key":"e_1_2_10_20_1","unstructured":"gnomAD browser PRPH2. 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