KCNH2 Duplication Variant (c.2164_2181dup) Associated With Sudden Cardiac Death in a Family With Congenital Long QT Syndrome.
Angela Ambrosio, Chai-Ann Ng, Lindsay Burnell et al.
✦ AI-curated · Sources linked
Case in brief
Postmortem genetic testing of a 34-year-old woman who died suddenly identified a KCNH2 variant of uncertain significance, c.2164_2181dup. Cascade testing found the same variant in her father and brother, both of whom had clinical evidence of congenital long QT syndrome. Calibrated automated patch-clamp analysis demonstrated a severe loss-of-function effect, providing strong functional evidence for reclassification. Considering this result alongside prior reports and the family’s phenotypes, the variant was reclassified as likely pathogenic.
What made this case unusual
The variant was initially classified as uncertain, but functional patch-clamp evidence, together with the family findings and previous reports, supported its reclassification as likely pathogenic.
Diagnostic / clinical pearl
A KCNH2 variant of uncertain significance may warrant functional assessment and family evaluation; here, patch-clamp evidence helped clarify its clinical significance.