ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.917G>A (p.Gly306Asp)

dbSNP: rs2101995501
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002001018 SCV002269442 uncertain significance Spinocerebellar ataxia type 19/22 2020-11-17 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with KCND3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 306 of the KCND3 protein (p.Gly306Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
Ambry Genetics RCV004043286 SCV003584912 uncertain significance Cardiovascular phenotype 2021-12-14 criteria provided, single submitter clinical testing The c.917G>A (p.G306D) alteration is located in exon 2 (coding exon 1) of the KCND3 gene. This alteration results from a G to A substitution at nucleotide position 917, causing the glycine (G) at amino acid position 306 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV002001018 SCV005042806 uncertain significance Spinocerebellar ataxia type 19/22 criteria provided, single submitter clinical testing The missense c.917G>A p.Gly306Asp variant in KCND3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly306Asp variant is novel not in any individuals in both gnomAD Exomes and 1000 Genomes databases. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Gly306Asp in KCND3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 306 is changed to a Asp changing protein sequence and it might alter its composition and physico-chemical properties. Another variant [c.901T>C p.Ser301Pro] in the nearby residue has been reported as disease causing, suggesting that this region might be a clinically significant domain. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.