ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1525C>T (p.Gln509Ter) (rs1184563885)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666347 SCV000790623 pathogenic Ceroid lipofuscinosis neuronal 2 2017-03-30 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000666347 SCV000891656 likely pathogenic Ceroid lipofuscinosis neuronal 2 2017-12-30 criteria provided, single submitter curation
Invitae RCV001386654 SCV001586966 pathogenic not provided 2020-09-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TPP1 gene (p.Gln509*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acids of the TPP1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with late-infantile neuronal ceroid lipofuscinosis (PMID: 10862088). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 551316). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001526988 SCV001737786 pathogenic Neuronal ceroid lipofuscinosis 2021-06-12 criteria provided, single submitter clinical testing Variant summary: TPP1 c.1525C>T (p.Gln509X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One study reports that this results in a mutant allele that is translated into a shorter peptide, lacking the last 54 amino acids of the encoded protein (Tessa_2000). The variant allele was found at a frequency of 1.2e-05 in 251456 control chromosomes. c.1525C>T has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (example, Tessa_2000). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as 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.