Submissions for variant NM_000219.6(KCNE1):c.374C>T (p.Thr125Met)

gnomAD frequency: 0.00027  dbSNP: rs142511345

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CSER _CC_NCGL, University of Washington	RCV000148513	SCV000190225	uncertain significance	Long QT syndrome	2014-06-01	criteria provided, single submitter	research	Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150856	SCV000198414	likely benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing	Thr125Met in exon 3 of KCNE1: This variant is not expected to have clinical sig nificance because the threonine (Thr) residue at position 125 is not conserved a cross species, with chimpanzee, gorilla, and four additional mammals having a me thionine (Met) at this position.
Illumina Laboratory Services, Illumina	RCV000321437	SCV000435782	likely benign	Jervell and Lange-Nielsen syndrome 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001094734	SCV000435784	likely benign	Long QT syndrome 5	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV001705874	SCV000728588	likely benign	not provided	2020-01-29	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24478792, 25637381, 24710009, 19716085, 26899768, 28988457, 29884292, 31941373)
Ambry Genetics	RCV000621107	SCV000736269	likely benign	Cardiovascular phenotype	2022-03-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000148513	SCV000752774	likely benign	Long QT syndrome	2024-01-12	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000119091	SCV000153810	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.
Clinical Genetics, Academic Medical Center	RCV001705874	SCV001921171	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001705874	SCV001972312	likely benign	not provided		no assertion criteria provided	clinical testing