ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.1703G>T (p.Gly568Val)

gnomAD frequency: 0.00018  dbSNP: rs71581017
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
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000414965 SCV000492727 uncertain significance Heart disease 2015-11-18 criteria provided, single submitter clinical testing
Invitae RCV000549875 SCV000646982 uncertain significance Atrial fibrillation, familial, 7 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 568 of the KCNA5 protein (p.Gly568Val). This variant is present in population databases (rs71581017, gnomAD 0.04%). This missense change has been observed in individual(s) with atrial fibrillation (AF) and in an unrelated individual with AF. However, in a separate study, this variant was not observed in any of the participants of an AF cohort and was only observed in several control individuals without a history of AF (PMID: 22402074, 23264583, 25410959). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374033). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNA5 function (PMID: 22402074). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000549875 SCV001370475 uncertain significance Atrial fibrillation, familial, 7 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance.
GeneDx RCV001662370 SCV001874831 uncertain significance not provided 2021-07-15 criteria provided, single submitter clinical testing Identified in several patients with atrial fibrillation as well as healthy controls in the published literature (Mann et al., 2012; Christophersen et al., 2013; Weeke et al., 2015), with this variant segregating with disease in one family (Mann et al 2012).; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 374033; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918, 27535533, 22402074, 25410959, 23264583)

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.