Submissions for variant NM_172056.2(KCNH2):c.1591C>T (p.Arg531Trp) (rs199472915)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000698598	SCV000827271	uncertain significance	Long QT syndrome	2019-10-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 531 of the KCNH2 protein (p.Arg531Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals referred for long QT syndrome genetic testing (PMID: 19716085, 28532774). ClinVar contains an entry for this variant (Variation ID: 67218). Experimental studies have shown that this missense change alters KCNH2 channel gating (PMID: 23546015). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust	RCV000057927	SCV000089447	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.