Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003305415 | SCV003997228 | uncertain significance | Cardiovascular phenotype | 2023-04-18 | criteria provided, single submitter | clinical testing | The p.E522K variant (also known as c.1564G>A), located in coding exon 6 of the KCND3 gene, results from a G to A substitution at nucleotide position 1564. The glutamic acid at codon 522 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003525384 | SCV004281429 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2023-05-11 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCND3 protein function. This variant has not been reported in the literature in individuals affected with KCND3-related conditions. This variant is present in population databases (rs749559538, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 522 of the KCND3 protein (p.Glu522Lys). |