Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620664 | SCV000738015 | uncertain significance | Cardiovascular phenotype | 2017-05-16 | criteria provided, single submitter | clinical testing | The p.A172T variant (also known as c.514G>A), located in coding exon 1 of the KCND3 gene, results from a G to A substitution at nucleotide position 514. The alanine at codon 172 is replaced by threonine, an amino acid with similar properties. 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. |
| Labcorp Genetics |
RCV001868114 | SCV002186234 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2024-06-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 172 of the KCND3 protein (p.Ala172Thr). This variant is present in population databases (rs149488365, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. ClinVar contains an entry for this variant (Variation ID: 519447). 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 with a negative predictive value of 80%. 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. |