Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498826 | SCV000590275 | uncertain significance | not provided | 2018-04-20 | criteria provided, single submitter | clinical testing | The T457M variant hasnot been published as pathogenic or been reported as benign to our knowledge. This variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. However, this substitution occursat a position that is not conserved across species, and M457 is the wild type amino acid in severalspecies. In silico analysis is inconsistent in its predictions as to whether or not the variant is damagingto the protein structure/function. In the ExAC dataset, T457M is observed in 4/38858 alleles and1/11176 alleles from individuals of European Non-Finnish and South Asian ancestry, respectively (Leket al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |
| Labcorp Genetics |
RCV001857017 | SCV002309685 | uncertain significance | Spinocerebellar ataxia type 19/22 | 2021-10-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with KCND3-related conditions. 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 432538). This variant is present in population databases (rs199637120, gnomAD 0.007%). This sequence change replaces threonine, a(n) neutral and polar amino acid, with methionine, a(n) neutral and non-polar amino acid, at codon 457 of the KCND3 protein (p.Thr457Met). |
| Fulgent Genetics, |
RCV002481586 | SCV002789704 | uncertain significance | Spinocerebellar ataxia type 19/22; Brugada syndrome 9 | 2021-10-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003302733 | SCV003993280 | likely benign | Cardiovascular phenotype | 2023-05-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000505597 | SCV000599865 | uncertain significance | Brugada syndrome 9 | 2017-04-20 | no assertion criteria provided | clinical testing |