Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department Of Translational Genomics |
RCV000171379 | SCV000221576 | uncertain significance | not provided | 2024-02-14 | criteria provided, single submitter | research | reclassified to VUS based on updated frequency (PMID: 31130284) |
| Gene |
RCV000171379 | SCV000573645 | uncertain significance | not provided | 2017-12-11 | criteria provided, single submitter | clinical testing | The E2419K variant of uncertain significance in the ANK2 gene has not been published as pathogenic or benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Furthermore, E2419K 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. This substitution also occurs at a position where only amino acids with similar properties to glutamate are tolerated across species. In addition, the majority of in silico tools predict E2419K is probably damaging the protein structure/function. Moreover, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with arrhythmia (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Invitae | RCV001852068 | SCV002278947 | uncertain significance | Long QT syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 191193). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is present in population databases (rs752704424, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2419 of the ANK2 protein (p.Glu2419Lys). |