Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
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, |
RCV000549875 | SCV001370475 | uncertain significance | Atrial fibrillation, familial, 7 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. |
Gene |
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) |