Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000640966 | SCV000762571 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2017-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with phenylalanine at codon 642 of the KCND3 protein (p.Ile642Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs754759010, ExAC 0.01%). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCND3-related disease. |
Ambry Genetics | RCV002406387 | SCV002717444 | uncertain significance | Cardiovascular phenotype | 2022-10-30 | criteria provided, single submitter | clinical testing | The p.I642F variant (also known as c.1924A>T), located in coding exon 7 of the KCND3 gene, results from an A to T substitution at nucleotide position 1924. The isoleucine at codon 642 is replaced by phenylalanine, 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. |