ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.1535A>C (p.Asp512Ala)

dbSNP: rs1664166577
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001890267 SCV002155561 uncertain significance Spinocerebellar ataxia type 19/22 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 512 of the KCND3 protein (p.Asp512Ala). This variant is not present in population databases (gnomAD no frequency). 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: 1382415). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCND3 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002397836 SCV002706191 uncertain significance Cardiovascular phenotype 2021-03-08 criteria provided, single submitter clinical testing The p.D512A variant (also known as c.1535A>C), located in coding exon 6 of the KCND3 gene, results from an A to C substitution at nucleotide position 1535. The aspartic acid at codon 512 is replaced by alanine, an amino acid with dissimilar properties. This variant was reported in an individual with progressive myoclonus epilepsy, who also had additional variants detected, including a novel homozygous NHLRC1 variant (Muona M et al. Nat Genet, 2015 Jan;47:39-46). 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.

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