ClinVar Miner

Submissions for variant NM_000310.4(PPT1):c.628-1G>T

gnomAD frequency: 0.00001  dbSNP: rs386833659
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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 2023-05-30 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: 56208). This variant is also known as IVS6-1G>T. Disruption of this splice site has been observed in individual(s) with infantile neuronal ceroid lipofuscinosis (PMID: 10679943). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the PPT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943, 21990111).
Revvity Omics, Revvity RCV000049619 SCV002019504 pathogenic Neuronal ceroid lipofuscinosis 1 2019-10-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000049619 SCV004204134 pathogenic Neuronal ceroid lipofuscinosis 1 2023-10-03 criteria provided, single submitter clinical testing
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.