Submissions for variant NM_000238.4(KCNH2):c.1834G>T (p.Val612Leu)

dbSNP: rs199472943

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002514286	SCV003440179	uncertain significance	Long QT syndrome	2023-05-01	criteria provided, single submitter	clinical testing	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. Experimental studies have shown that this missense change affects KCNH2 function (PMID: 11524404, 16432067). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 67291). This missense change has been observed in individual(s) with long QT syndrome (PMID: 9544837). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 612 of the KCNH2 protein (p.Val612Leu).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058008	SCV000089528	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:9544837;PMID:16432067). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.