Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000432369 | SCV000526317 | uncertain significance | not provided | 2016-03-28 | criteria provided, single submitter | clinical testing | A novel variant of uncertain significance has been identified in the ANK2 gene. The E3800K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E3800K variant 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. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Labcorp Genetics |
RCV001042464 | SCV001206146 | uncertain significance | Long QT syndrome | 2019-11-26 | 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"). This variant has not been reported in the literature in individuals with ANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 385149). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 3800 of the ANK2 protein (p.Glu3800Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
Ambry Genetics | RCV002323622 | SCV002605753 | uncertain significance | Cardiovascular phenotype | 2021-12-29 | criteria provided, single submitter | clinical testing | The p.E3800K variant (also known as c.11398G>A), located in coding exon 43 of the ANK2 gene, results from a G to A substitution at nucleotide position 11398. The glutamic acid at codon 3800 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on its frequency in gnomAD, this variant is unlikely to be causative of ANK2-related arrhythmia; however, its clinical significance for ANK2-related neurodevelopmental disorder is unclear. |
Fulgent Genetics, |
RCV002480308 | SCV002778815 | uncertain significance | Cardiac arrhythmia, ankyrin-B-related | 2021-11-11 | criteria provided, single submitter | clinical testing |