Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002387805 | SCV002692377 | uncertain significance | Cardiovascular phenotype | 2021-10-21 | criteria provided, single submitter | clinical testing | The p.L449F variant (also known as c.1345C>T), located in coding exon 3 of the KCND3 gene, results from a C to T substitution at nucleotide position 1345. The leucine at codon 449 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Labcorp Genetics |
RCV003095006 | SCV003444914 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2022-03-19 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.1%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 449 of the KCND3 protein (p.Leu449Phe). |