Submissions for variant NM_000391.4(TPP1):c.1547_1548del (p.Leu515_Phe516insTer)

dbSNP: rs763961289

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668676	SCV000793314	uncertain significance	Neuronal ceroid lipofuscinosis 2	2017-08-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388426	SCV001589411	pathogenic	not provided	2022-08-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TPP1 protein in which other variant(s) (p.Trp542*) have been determined to be pathogenic (PMID: 31283065; 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: 553269). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21990111, 30541466). This variant is present in population databases (rs763961289, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe516*) in the TPP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the TPP1 protein.
Revvity Omics, Revvity	RCV001388426	SCV003820435	pathogenic	not provided	2022-11-13	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000668676	SCV002094796	pathogenic	Neuronal ceroid lipofuscinosis 2	2021-04-13	no assertion criteria provided	clinical testing