Amino acid-level signal-to-noise analysis of incidentally identified variants in genes associated with long QT syndrome during pediatric whole exome sequencing reflects background genetic noise

摘要

BackgroundDue to rapid expansion of clinical genetic testing, an increasing number of genetic variants of undetermined significance are being identified in children with unclear diagnostic value. Variants found in genes associated with heritable channelopathies, such as long QT syndrome (LQTS), are particularly difficult to interpret given the risk of sudden cardiac death associated with pathologic mutations. Objective: To determine whether variants in LQTS-associated genes from whole exome sequencing (WES) represent disease-associated biomarkers or background genetic “noise.”