ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.665T>C (p.Leu222Pro) (rs386833661)

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
Integrated Genetics/Laboratory Corporation of America RCV001192781 SCV001361119 pathogenic Neuronal ceroid lipofuscinosis 2019-11-01 criteria provided, single submitter clinical testing Variant summary: PPT1 c.665T>C (p.Leu222Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 31368 control chromosomes. c.665T>C has been reported in the literature in multiple individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Mazzei_2002, Simonati_2009, Santorelli_2013). These data indicate that the variant is very likely to be associated with disease. Simonati et al report that this mutation occurs in the hydrophobic pouch of PPT-1, and the introduction of a proline may hamper the correct folding and therefore the beta-sheet conformation of the protein (Simonati_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049621 SCV000082028 probable-pathogenic Neuronal ceroid lipofuscinosis 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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.