Submissions for variant NM_000218.3(KCNQ1):c.1455C>T (p.Phe485=)

gnomAD frequency: 0.01545  dbSNP: rs17215465

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035341	SCV000058989	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	"Phe485Phe in Exon 11 of KCNQ1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 4.6% (171/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs17215465)."
Ambry Genetics	RCV000252365	SCV000318476	benign	Cardiovascular phenotype	2015-08-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Illumina Laboratory Services, Illumina	RCV001093940	SCV000370336	benign	Long QT syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000347940	SCV000370337	likely benign	Atrial fibrillation, familial, 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000394385	SCV000370338	benign	Short QT syndrome type 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000308018	SCV000370339	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000341890	SCV000370340	benign	Jervell and Lange-Nielsen syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000290497	SCV000555813	benign	Long QT syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589971	SCV000695986	benign	not provided	2016-09-06	criteria provided, single submitter	clinical testing	Variant summary: The KCNQ1 c.1455C>T (p.Phe485Phe) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 737/121388 control chromosomes (15 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0483468 (503/10404). This frequency is about 483 times the estimated maximal expected allele frequency of a pathogenic KCNQ1 variant (0.0001), indicating this is a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory as well as publications classified this variant as benign. Taken together, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV001841557	SCV000910819	benign	Cardiac arrhythmia	2018-03-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589971	SCV001159386	benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000589971	SCV001845583	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000290497	SCV004836442	benign	Long QT syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035341	SCV001923411	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035341	SCV001953006	benign	not specified		no assertion criteria provided	clinical testing