ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.481C>T (p.Gln161Ter)

gnomAD frequency: 0.00001  dbSNP: rs764256845
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
Invitae RCV001065769 SCV001230752 pathogenic not provided 2023-06-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 859613). This premature translational stop signal has been observed in individual(s) with TPP1-related conditions (PMID: 31283065). This variant is present in population databases (rs764256845, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Gln161*) in the TPP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPP1 are known to be pathogenic (PMID: 10330339).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265936 SCV002548006 likely pathogenic Neuronal ceroid lipofuscinosis 2022-05-11 criteria provided, single submitter clinical testing Variant summary: TPP1 c.481C>T (p.Gln161X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251446 control chromosomes (gnomAD). c.481C>T has been reported in the literature in individual(s) affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Gardner_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002497463 SCV002809875 likely pathogenic Neuronal ceroid lipofuscinosis 2; Autosomal recessive spinocerebellar ataxia 7 2021-12-07 criteria provided, single submitter clinical testing

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.