ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.4652G>A (p.Arg1551Gln) (rs376658420)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517273 SCV000613917 uncertain significance not provided 2018-05-08 criteria provided, single submitter clinical testing
Invitae RCV000639790 SCV000761371 uncertain significance Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Mental retardation, autosomal dominant 9 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1551 of the KIF1A protein (p.Arg1551Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs376658420, ExAC 0.09%). This variant has not been reported in the literature in individuals with KIF1A-related disease. ClinVar contains an entry for this variant (Variation ID: 447657). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000718224 SCV000849086 uncertain significance History of neurodevelopmental disorder 2017-03-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000517273 SCV000885634 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing The p.Arg1551Gln variant (rs376658420) has not been reported in the medical literature and is not listed in gene-specific variant databases. It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in Latino populations of 0.082% (identified in 28 out of 34,234 chromosomes). The arginine at codon 1551 is moderately conserved considering 13 species (Alamut software v2.9), and computational analyses suggest this variant does not have a significant effect on KIF1A protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Arg1551Gln variant cannot be determined with certainty.
Fulgent Genetics,Fulgent Genetics RCV000764391 SCV000895444 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Mental retardation, autosomal dominant 9 2018-10-31 criteria provided, single submitter clinical testing

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.