ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.1888C>G (p.Gln630Glu) (rs200171609)

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
GeneDx RCV000188754 SCV000242378 uncertain significance not provided 2017-07-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRICKLE1 gene. The Q630E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations but the 1000 Genomes Project reports Q630E was observed in 1/162 (0.5%) alleles from individuals of Punjabi background. The Q630E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000375035 SCV000378696 uncertain significance Progressive myoclonus epilepsy with ataxia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000375035 SCV000551472 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 630 of the PRICKLE1 protein (p.Gln630Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs200171609, ExAC 0.09%) but has not been reported in the literature in individuals with a PRICKLE1-related disease. ClinVar contains an entry for this variant (Variation ID: 206676). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, 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.