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A limiting factor is the quality of available phenotypic data. Here, we describe how deep clinicopathological phenotyping yielded a molecular diagnosis for a 19\u2010year\u2010old proband with muscular dystrophy and negative clinical ES. Deep phenotypic analysis identified two critical data points: (1) the absence of emerin protein in muscle biopsy and (2) clinical features consistent with Emery\u2010Dreifuss muscular dystrophy. Sequencing data analysis uncovered an ultra\u2010rare, intronic variant in <jats:italic>EMD<\/jats:italic>, the gene encoding emerin. The variant, NM_000117.3: c.188\u20106A\u00a0&gt;\u00a0G, is predicted to impact splicing by <jats:italic>in silico<\/jats:italic> tools. This case thus illustrates how better integration of clinicopathologic data into ES analysis can enhance diagnostic yield with implications for clinical practice.<\/jats:p>","DOI":"10.1002\/acn3.51454","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:36:24Z","timestamp":1631709384000},"page":"2052-2058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep clinicopathological phenotyping identifies a previously unrecognized pathogenic <i>EMD<\/i> splice variant"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-372X","authenticated-orcid":false,"given":"Daniel G.","family":"Calame","sequence":"first","affiliation":[{"name":"Division of Neurology and Developmental Neuroscience Department of Pediatrics Baylor College of Medicine Houston Texas 77030 USA"},{"name":"Texas Children\u2019s Hospital Houston Texas 77030 USA"},{"name":"Department 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