Submissions for variant NM_172057.2(KCNH2):c.2083C>T (p.Arg695Trp) (rs199473543)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000473177	SCV000543412	uncertain significance	Long QT syndrome	2018-07-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 1035 of the KCNH2 protein (p.Arg1035Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNH2-related disease. However, it has been reported in a healthy control individual (PMID: 14661677). ClinVar contains an entry for this variant (Variation ID: 67468). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust	RCV000058196	SCV000089716	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:14661677;PMID:19841300).