Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001203107 | SCV001374254 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2023-04-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs774713377, gnomAD 0.009%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 934670). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 630 of the KCND3 protein (p.Arg630Gln). |
| Ambry Genetics | RCV002411741 | SCV002723851 | uncertain significance | Cardiovascular phenotype | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.R630Q variant (also known as c.1889G>A), located in coding exon 7 of the KCND3 gene, results from a G to A substitution at nucleotide position 1889. The arginine at codon 630 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Fulgent Genetics, |
RCV002504232 | SCV002816595 | uncertain significance | Spinocerebellar ataxia type 19/22; Brugada syndrome 9 | 2021-11-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003148945 | SCV003837252 | uncertain significance | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768909 | SCV005380363 | uncertain significance | not specified | 2024-08-22 | criteria provided, single submitter | clinical testing | Variant summary: KCND3 c.1889G>A (p.Arg630Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251314 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1889G>A in individuals affected with Spinocerebellar Ataxia Type 19/22 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 934670). Based on the evidence outlined above, the variant was classified as uncertain significance. |