Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001368781 | SCV001565192 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2021-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 545 of the KCND3 protein (p.Thr545Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KCND3-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV004037058 | SCV003653954 | uncertain significance | Cardiovascular phenotype | 2023-07-28 | criteria provided, single submitter | clinical testing | The p.T545I variant (also known as c.1634C>T), located in coding exon 6 of the KCND3 gene, results from a C to T substitution at nucleotide position 1634. The threonine at codon 545 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |