Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001890267 | SCV002155561 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2022-04-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 512 of the KCND3 protein (p.Asp512Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. |
| Ambry Genetics | RCV002397836 | SCV002706191 | uncertain significance | Cardiovascular phenotype | 2021-03-08 | criteria provided, single submitter | clinical testing | The p.D512A variant (also known as c.1535A>C), located in coding exon 6 of the KCND3 gene, results from an A to C substitution at nucleotide position 1535. The aspartic acid at codon 512 is replaced by alanine, an amino acid with dissimilar properties. This variant was reported in an individual with progressive myoclonus epilepsy, who also had additional variants detected, including a novel homozygous NHLRC1 variant (Muona M et al. Nat Genet, 2015 Jan;47:39-46). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |