Submissions for variant NM_172056.2(KCNH2):c.245T>C (p.Ile82Thr) (rs1563189895)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine	RCV000709728	SCV000839966	likely pathogenic	Long QT syndrome 2	2017-06-05	criteria provided, single submitter	clinical testing	This c.245T>C (p.Ile82Thr) variant in the KCNH2 gene has previously been reported in dizigotic twins with long QT syndrome (LQTS) and a history of epilepsy controlled under medication [PMID 23899126]. The mother and grandmother had LQTS and died suddendly in their 20s. One of the twins died suddendly at 18 y/o and the sister underwent implantation of a cardioverter-defibrillator. Functional studies for this variant revealed a severe reduction in current density and modifications of gating properties, indicating a loss of function mechanism. This variant is not present in the ExAC population database and has not been previously observed in our patient's cohort. Isoleucine at amino acid position 82 of the KCNH2 protein is moderately conserved in mammals. While not clinically validated, computer-based algorithms predict this p.Ile82Thr change to be deleterious. It is thus interpreted as a likely pathogenic variant.