Show description/summary:1) This variant alters protein function, but is it pathogenic? (Neurology® Genetics)2) What’s Trending: PFO UpdatesThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the November 7, 2017 issue of Neurology. In the first segment, Dr. Michelle Mauermann talks with Dr. Massimo Pandolfo about his recent Neurology® Genetics editorial, entitled “This variant alters protein function, but is it pathogenic?”. In the second part of the podcast, Dr. Nicole Chiota focuses her interview with Dr. Steven Messe on recent PFO/stroke updates. Disclosures can be found at Neurology.org.DISCLOSURES: Dr. Mauermann serves on the editorial board of Mayo Clinic Proceedings; receives publishing royalties from Oxford, and has received research support from Ionis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals.Dr. Pandolfo has served on the scientific advisory boards of Apopharma and Voyager Therapeutics; has served on the editorial boards of Acta Neurologica Belgica, Orphanet Journal of Rare Diseases, and Neurology Genetics; is co-holder of a patent for Direct molecular diagnosis of Friedreich’s ataxia; has been a consultant for Biomarin and UCB; has received research support from Biomarin, Fonds National de la Recherche Scientifique (Belgium), Offrez-moi-la-lune, Friedreich's Ataxia Research Alliance, and Association Belge contre les Maladies neuro-Musculaires, and receives royalty payments from Athena Diagnositcs for a Friedreich's ataxia diagnostic test.Dr. Chiota reports no disclosures.Dr. Messe has served on the scientific advisory board of the Yale University Cardiovascular Research Group; has received travel funding from the American Academy of Neurology; has received publishing royalties from Up To Date; has been a consultant for Claret Medical; and has received research support from WL Gore, Glaxo Smith Kline, Bayer, Mallinkrodt, and NIH.