Submissions for variant NM_000218.3(KCNQ1):c.619G>A (p.Val207Met)

gnomAD frequency: 0.00091  dbSNP: rs75813654

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035348	SCV000058996	likely benign	not specified	2012-12-19	criteria provided, single submitter	clinical testing	Val207Met in exon 4 of KCNQ1: This variant was initially identified in 1/17 indi viduals with sudden unexplained death and in 0.01% (2/1188) control chromosomes (Ackerman 2003, Nishio 2009). Although a mouse model showed prolonged-QT interva ls with homozygosity of the variant (Nishio 2009), clinical disease was not docu mented. Follow-up studies showed that function of the Val207Met KCNQ1 protein is comparable to wild-type (Eldstrom 2010). In addition, the variant has subsequen tly been observed in 0.3% (14/4402) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project as well as 1.7% (3/176) of ind ividuals of Yoruba descent (http://evs.gs.washington.edu/EVS/; dbSNP rs75813654) . Furthermore, the Val207 residue is not conserved in mammals suggesting a misse nse variant may be less impactful of protein function. In summary, based on func tional studies, lack of conservation and high allele frequencies in the general population, this variant is likely benign.
GeneDx	RCV000057724	SCV000234398	likely benign	not provided	2021-05-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20421371, 22949429, 25119684, 14661677, 19841300, 29532034, 29557500, 28988457, 30571187, 19198868, 32797034)
Invitae	RCV001083578	SCV000555808	likely benign	Long QT syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000057724	SCV000610937	likely benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841562	SCV001349847	likely benign	Cardiac arrhythmia	2019-01-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000057724	SCV002049379	likely benign	not provided	2020-10-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003914917	SCV004729158	likely benign	KCNQ1-related condition	2023-06-13	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057724	SCV000089243	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:14661677;PMID:19198868;PMID:19841300).
Clinical Genetics, Academic Medical Center	RCV000057724	SCV001925144	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000057724	SCV001929629	likely benign	not provided		no assertion criteria provided	clinical testing