Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000492796 | SCV000582601 | uncertain significance | not provided | 2017-05-15 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ANK2 gene. The V2686A variant has not been published as pathogenic or been reported as benign to our knowledge. Additionally, 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). While this substitution occurs at a position that is conserved in mammals, alanine (A) is the wild-type residue at this position in at least one non-mammalian species. Additionally, V2686A is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Ambry Genetics | RCV002413357 | SCV002675869 | likely benign | Cardiovascular phenotype | 2019-10-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV002527094 | SCV002962261 | uncertain significance | Long QT syndrome | 2024-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2686 of the ANK2 protein (p.Val2686Ala). This variant is present in population databases (rs56095304, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 429915). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |