Clinical interpretation of KCNH2 variants using a robust PS3/BS3 functional patch-clamp assay.

ABSTRACT: Long QT syndrome (LQTS), caused by the dysfunction of cardiac ion channels, increases the risk of sudden death in otherwise healthy young people. For many variants in LQTS genes, there is insufficient evidence to make a definitive genetic diagnosis. We have established a robust functional patch-clamp assay to facilitate classification of missense variants in KCNH2, one of the key LQTS genes. A curated set of 30 benign and 30 pathogenic missense variants were used to establish the range of normal and abnormal function. The extent to which variants reduced protein function was quantified using Z scores, the number of standard deviations from the mean of the normalized current density of the set of benign variant controls. A Z score of -2 defined the threshold for abnormal loss of function, w

SUBMITTER: Thomson KL 

PROVIDER: S-EPMC10840334 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature