ClinVar Miner

Submissions for variant NM_024790.6(CSPP1):c.1678G>A (p.Val560Ile) (rs199608505)

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
GeneDx RCV000521993 SCV000617040 uncertain significance not provided 2016-08-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CSPP1 gene. The V560I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V560I variant was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in an external variant database, but the 1000 Genomes Project reports it was observed in 2/1006 (0.2%) alleles from individuals of European background. The V560I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000703453 SCV000832352 uncertain significance Joubert syndrome 21 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 560 of the CSPP1 protein (p.Val560Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs199608505, ExAC 0.1%). This variant has not been reported in the literature in individuals with CSPP1-related disease. ClinVar contains an entry for this variant (Variation ID: 449196). 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 isoleucine 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. 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.

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.