Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001922966 | SCV002183559 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2023-04-16 | 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. ClinVar contains an entry for this variant (Variation ID: 1411863). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. This variant is present in population databases (rs778141653, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 550 of the KCND3 protein (p.Arg550Cys). |
| Ambry Genetics | RCV004043343 | SCV003539244 | uncertain significance | Cardiovascular phenotype | 2024-05-04 | criteria provided, single submitter | clinical testing | The p.R550C variant (also known as c.1648C>T), located in coding exon 6 of the KCND3 gene, results from a C to T substitution at nucleotide position 1648. The arginine at codon 550 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |