Submissions for variant NM_000310.4(PPT1):c.722C>T (p.Ser241Leu)

gnomAD frequency: 0.00001  dbSNP: rs746043871

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179745	SCV000232044	uncertain significance	not provided	2015-02-23	criteria provided, single submitter	clinical testing
Counsyl	RCV000670818	SCV000795722	uncertain significance	Neuronal ceroid lipofuscinosis 1	2017-11-13	criteria provided, single submitter	clinical testing
Invitae	RCV000670818	SCV001202337	pathogenic	Neuronal ceroid lipofuscinosis 1	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 241 of the PPT1 protein (p.Ser241Leu). This variant is present in population databases (rs746043871, gnomAD 0.01%). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 22387303, 23374165; Invitae). ClinVar contains an entry for this variant (Variation ID: 198413). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PPT1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000670818	SCV004100702	likely pathogenic	Neuronal ceroid lipofuscinosis 1	2023-09-19	criteria provided, single submitter	clinical testing	Criteria applied: PS4_MOD,PM1,PM2_SUP,PP3
Baylor Genetics	RCV000670818	SCV004204146	likely pathogenic	Neuronal ceroid lipofuscinosis 1	2024-03-17	criteria provided, single submitter	clinical testing