Submissions for variant NM_000218.3(KCNQ1):c.1135T>C (p.Trp379Arg)

dbSNP: rs199472768

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000505766	SCV000234482	uncertain significance	not provided	2024-09-06	criteria provided, single submitter	clinical testing	Reported in association with LQTS (PMID: 16534005, 17222736, 26066609); Not observed at significant frequency in large population cohorts (gnomAD); While in vitro functional studies suggest that this variant may impact channel function; however, it is unclear how these studies may translate to a pathogenic role in vivo (PMID: 26066609); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31535183, 22677073, 17222736, 26066609, 31892348, 22581653, 16534005)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000462343	SCV000543319	pathogenic	Long QT syndrome	2022-11-08	criteria provided, single submitter	clinical testing	Experimental studies have shown that this missense change affects KCNQ1 function (PMID: 26066609). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 379 of the KCNQ1 protein (p.Trp379Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with long QT syndrome (PMID: 16534005, 26066609; Invitae). ClinVar contains an entry for this variant (Variation ID: 67013). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ1 protein function. For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000462343	SCV000747934	pathogenic	Long QT syndrome	2016-05-31	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057559	SCV000089078	not provided	SUDDEN INFANT DEATH SYNDROME		no assertion provided	literature only	This variant has been reported as associated with Sudden infant death syndrome in the following publications (PMID:17222736;PMID:22677073). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.