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Meanwhile, <jats:italic>KCNJ2<\/jats:italic>, encoding inward\u2010rectifier potassium channel (I<jats:sub>K1<\/jats:sub>), can be the responsible gene for atypical CPVT. We recently encountered a family with CPVT and sought to identify a responsible gene variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A targeted panel sequencing (TPS) was employed in the proband. Copy number variation (CNV) in <jats:italic>RYR2<\/jats:italic> was identified by focusing on read numbers in the TPS and long\u2010range PCR. Cascade screening was conducted by a Sanger method and long\u2010range PCR. KCNJ2 wild\u2010type (WT) or an identified variant was expressed in COS\u20101 cells, and whole\u2010cell currents (I<jats:sub>K1<\/jats:sub>) were recorded using patch\u2010clamp techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 40\u2010year\u2010old female experienced cardiopulmonary arrest while cycling. Her ECG showed sinus bradycardia with prominent U\u2010waves (\u22650.2\u00a0mV). She had left ventricular hypertrabeculation at apex. Exercise induced frequent polymorphic ventricular arrhythmias. Her sister died suddenly at age 35 while bouldering. Her father and paternal aunt, with prominent U\u2010waves, received permanent pacemaker due to sinus node dysfunction. The initial TPS and cascade screening identified a <jats:italic>KCNJ2<\/jats:italic> E118D variant in all three symptomatic patients. However, after focusing on read numbers, we identified a novel exon3 deletion of <jats:italic>RYR2<\/jats:italic> (<jats:italic>RYR2<\/jats:italic>\u2010exon3 deletion) in all of them. Functional analysis revealed that KCNJ2 E118D generated I<jats:sub>K1<\/jats:sub> indistinguishable from KCNJ2 WT, even in the presence of catecholaminergic stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Focusing on the read numbers in the TPS enabled us to identify a novel CNV, <jats:italic>RYR2<\/jats:italic>\u2010exon3 deletion, which was associated with phenotypic features of this family.<\/jats:p><\/jats:sec>","DOI":"10.1111\/anec.12623","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T22:39:41Z","timestamp":1546987181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of a novel exon3 deletion of <i>RYR2<\/i> in a family with catecholaminergic polymorphic ventricular tachycardia"],"prefix":"10.1111","volume":"24","author":[{"given":"Tommy","family":"Dharmawan","sequence":"first","affiliation":[{"name":"Department 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