ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.628-1G>T (rs386833659)

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 RCV000049619 SCV000485573 likely pathogenic Neuronal ceroid lipofuscinosis 1 2016-01-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587410 SCV000696511 pathogenic Neuronal ceroid lipofuscinosis 2016-05-06 criteria provided, single submitter clinical testing Variant summary: The c.628-1G>T in a PPT1 gene is a splice-site variant that alters a conserved nucleotide. 5/5 in silico tools in Alamut predict this variant to disrupt a canonical acceptor sequence, however these predictions have yet to be confirmed by functional assay. The variant is absent from ExAC but has been reported in multiple affected patients presented with infantile neuronal ceroid lipofuscinoses. In addition, a reputable database/diagnostic center classified the variant of interest as Likely Pathogenic. Taken together, the variant was classified as pathogenic.
Invitae RCV000049619 SCV001217722 pathogenic Neuronal ceroid lipofuscinosis 1 2020-01-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 of the PPT1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with infantile neuronal ceroid lipofuscinosis (PMID: 10679943). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS6-1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 56208). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049619 SCV000082026 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.