ClinVar Miner

Submissions for variant NM_001365951.3(KIF1B):c.2605G>A (p.Glu869Lys)

gnomAD frequency: 0.00002  dbSNP: rs370243199
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001359409 SCV001555279 uncertain significance Charcot-Marie-Tooth disease type 2 2020-07-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 823 of the KIF1B protein (p.Glu823Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs370243199, ExAC 0.001%). This variant has not been reported in the literature in individuals with KIF1B-related conditions. 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 tolerated, 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.
Ambry Genetics RCV002456542 SCV002736188 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-01 criteria provided, single submitter clinical testing The p.E823K variant (also known as c.2467G>A), located in coding exon 23 of the KIF1B gene, results from a G to A substitution at nucleotide position 2467. The glutamic acid at codon 823 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003120581 SCV003800466 uncertain significance not provided 2022-09-15 criteria provided, single submitter clinical testing The KIF1B c.2467G>A; p.Glu823Lys variant (rs370243199), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1051384). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamate at codon 823 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.314). Due to limited information, the clinical significance of the p.Glu823Lys variant is uncertain at this time.

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