Submissions for variant NM_000310.4(PPT1):c.776dup (p.Glu260fs)

gnomAD frequency: 0.00001  dbSNP: rs1349528345

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000673195	SCV000798371	likely pathogenic	Neuronal ceroid lipofuscinosis 1	2018-03-08	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000673195	SCV001870333	pathogenic	Neuronal ceroid lipofuscinosis 1	2020-10-30	criteria provided, single submitter	research	ACMG codes:PVS1, PM2, PM3
Labcorp Genetics (formerly Invitae), Labcorp	RCV000673195	SCV002247163	pathogenic	Neuronal ceroid lipofuscinosis 1	2022-06-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PPT1 protein in which other variant(s) (p.Leu271*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 557103). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 23857568). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu260Glyfs*35) in the PPT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acid(s) of the PPT1 protein.