G C A T T A C G G C A T genes Article An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data Valentina Cipriani 1,2,3,4,* , Nikolas Pontikos 2,3 , Gavin Arno 2,3,5, Panagiotis I. Sergouniotis 6 , Eva Lenassi 6, Penpitcha Thawong 7, Daniel Danis 8 , Michel Michaelides 2,3, Andrew R. Webster 2,3, Anthony T. Moore 2,3,9, Peter N. Robinson 8 , Julius O.B. Jacobsen 1 and Damian Smedley 1 1 William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK;
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[email protected] (D.S.) 2 UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK;
[email protected] (N.P.);
[email protected] (G.A.);
[email protected] (M.M.);
[email protected] (A.R.W.);
[email protected] (A.T.M.) 3 Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK 4 UCL Genetics Institute, University College London, London WC1E 6AA, UK 5 North East Thames Regional Genetics Laboratory, Great Ormond Street Hospital NHS Trust, London WC1N 3BH, UK 6 Manchester Royal Eye Hospital & University of Manchester, Manchester M13 9WL, UK;
[email protected] (P.I.S.);
[email protected] (E.L.) 7 Department of Medical Sciences, Medical Genetics Section, National Institute of Health, Ministry of Public Health, Nonthaburi 11000, Thailand;
[email protected] 8 The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA;
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[email protected] (P.N.R.) 9 Ophthalmology Department, UCSF School of Medicine, San Francisco, CA 94143-0644, USA * Correspondence:
[email protected]; Tel.: +44-(0)207-882-2096 Received: 11 March 2020; Accepted: 16 April 2020; Published: 23 April 2020 Abstract: Next-generation sequencing has revolutionized rare disease diagnostics, but many patients remain without a molecular diagnosis, particularly because many candidate variants usually survive despite strict filtering.