ClinVar Miner

Submissions for variant NM_002234.4(KCNA5):c.1703G>T (p.Gly568Val) (rs71581017)

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Total submissions: 3
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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 2020-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 568 of the KCNA5 protein (p.Gly568Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs71581017, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in a family affected with atrial fibrillation (AF) (PMID: 22402074) and in an unrelated individual with AF (PMID: 23264583). 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: 25410959). ClinVar contains an entry for this variant (Variation ID: 374033). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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