ClinVar Miner

Submissions for variant NM_003159.2(CDKL5):c.2980G>A (p.Gly994Arg) (rs866859766)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neurogenetics Laboratory - MEYER,AOU Meyer RCV000416997 SCV000494567 uncertain significance Epileptic encephalopathy 2016-11-16 criteria provided, single submitter clinical testing
Invitae RCV000466195 SCV000547676 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2016-06-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 994 of the CDKL5 protein (p.Gly994Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. It also falls at the last nucleotide of exon 20 of the CDKL5 coding sequence. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDKL5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The arginine 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. Nucleotide substitutions at the last nucleotide of the exon are relatively common causes of aberrant splicing (PMID: 17576681) but according to multiple splice site algorithms this particular variant is not predicted to significantly affect splicing. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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.