ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.1646G>A (p.Arg549His)

gnomAD frequency: 0.00016  dbSNP: rs35027371
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000243000 SCV000320526 likely benign Cardiovascular phenotype 2022-12-07 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.
Invitae RCV000696815 SCV000825394 uncertain significance Spinocerebellar ataxia type 19/22 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 549 of the KCND3 protein (p.Arg549His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs35027371, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). 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: 264530). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV000696815 SCV001519148 likely pathogenic Spinocerebellar ataxia type 19/22 2021-07-12 criteria provided, single submitter research

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