ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.1703G>A (p.Arg568His)

gnomAD frequency: 0.00007  dbSNP: rs200212002
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000640964 SCV000762569 uncertain significance Spinocerebellar ataxia type 19/22 2023-05-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 568 of the KCND3 protein (p.Arg568His). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCND3 protein function. ClinVar contains an entry for this variant (Variation ID: 533722). This variant has not been reported in the literature in individuals affected with KCND3-related conditions. This variant is present in population databases (rs200212002, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant.
GeneDx RCV001563036 SCV001785907 uncertain significance not provided 2024-06-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002397224 SCV002710450 likely benign Cardiovascular phenotype 2024-02-26 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.

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