ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1381A>T (p.Ile461Phe) (rs794728536)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182222 SCV000234525 likely pathogenic not provided 2014-07-18 criteria provided, single submitter clinical testing p.Ile588Phe (ATC>TTC): c.1762 A>T in exon 15 of the KCNQ1 gene (NM_000218.2). A I588F variant that is likely pathogenic was identified in the KCNQ1 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The I588F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I588F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is class conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (R583H, N586S, T587M, G589D, A590T) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in LQT panel(s).
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000234786 SCV000240224 pathogenic Long QT syndrome 1 2012-01-01 criteria provided, single submitter research
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000234786 SCV001435328 likely pathogenic Long QT syndrome 1 2020-05-17 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.