ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.1427A>G (p.His476Arg)

gnomAD frequency: 0.00001  dbSNP: rs1571626155
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000992220 SCV001144304 uncertain significance not provided 2019-05-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001214863 SCV001386568 uncertain significance Spinocerebellar ataxia type 19/22 2023-10-07 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 476 of the KCND3 protein (p.His476Arg). 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: 804952). 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. 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 RCV002391049 SCV002698449 uncertain significance Cardiovascular phenotype 2024-03-19 criteria provided, single submitter clinical testing The p.H476R variant (also known as c.1427A>G), located in coding exon 4 of the KCND3 gene, results from an A to G substitution at nucleotide position 1427. The histidine at codon 476 is replaced by arginine, an amino acid with highly similar properties. 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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