ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1551+1G>C (rs786204553)

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
Counsyl RCV000411444 SCV000485467 likely pathogenic Ceroid lipofuscinosis neuronal 2 2015-12-15 criteria provided, single submitter clinical testing
Invitae RCV001038809 SCV001202305 uncertain significance Neuronal ceroid lipofuscinosis 2019-12-06 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 12) of the TPP1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in combination with another TPP1 variant in individuals affected with late infantile neuronal ceroid lipofuscinosis (PMID: 20820830, 26032578). ClinVar contains an entry for this variant (Variation ID: 370214). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.