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

gnomAD frequency: 0.00001  dbSNP: rs386833659

Total submissions: 6

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.