ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1480G>A (p.Gly494Ser) (rs199472820)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471820 SCV000543320 uncertain significance Long QT syndrome 2016-09-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 621 of the KCNQ1 protein (p.Gly621Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs199472820, ExAC <0.01%). This variant has been reported in an individual who experienced sudden cardiac death (PMID: 25447171). It has also been observed in an individual without a known history of arrhythmias (PMID: 14661677). ClinVar contains an entry for this variant (Variation ID: 67061). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The serine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on mRNA splicing. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000484989 SCV000568142 uncertain significance not specified 2017-03-22 criteria provided, single submitter clinical testing The G621S variant in the KCNQ1 gene has been published in an 11-month-old male with sudden cardiac death during sleeping. However, this individual harbored several cardiogenetic variants, including a TTN variant predicted to be disease-causing (Campuzano et al.,2014). The G621S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Finally, although G621S is not observed at a significant frequency in large population cohorts, it has been reported as a rare control variant in at least one ostensibly healthy Black individual (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server; Ackerman et al., 2003; Kapa et al., 2009; Giudicessi et al., 2012).
Fulgent Genetics,Fulgent Genetics RCV000763730 SCV000894614 uncertain significance Atrial fibrillation, familial, 3; Beckwith-Wiedemann syndrome; Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057646 SCV000089165 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:14661677;PMID:19841300).

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.