Submission Details

ANK2 encodes Ankyrin2, a protein important for localization and membrane stabilization of cardiac ion channels. This gene is located within a very large (~16 million bp) region identified by linkage analysis in a large family with LQTS (PMID 7485162). Subsequent sequencing of ANK2 in members of this family identified a missense variant (p.Glu1458Gly) that at time of publication (2003, PMID 12571597) was thought to be pathogenic. Contemporary data, however, demonstrates this variant has a population frequency too high for an autosomal dominant cause of LQTS (~1:400 individuals of Latino ancestry). Due to lack of other segregation data or case-control data and paucity of additional genetic and experimental data, this gene-disease association was classified as disputed. Note: All LQTS genes were curated by 3 separate blinded teams. The evidence and scores reached by these 3 teams was reviewed by the LQTS Clinical Domain Working Group. The classification and summary presented here is the conclusion of this Working Group's analysis according to evidence available at time of publication. The scores presented here are the result of only one of the three curation teams' efforts. For a detailed discussion of this group's work and the scores of all 3 teams please see "Adler et al. An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome. Circulation 2020;141(6):418-428. doi: 10.1161/CIRCULATIONAHA.119.043132”