Submissions for variant NM_006493.4(CLN5):c.466C>T (p.Pro156Ser)

dbSNP: rs386833977

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000049954	SCV000594153	likely pathogenic	Neuronal ceroid lipofuscinosis 5	2015-08-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853061	SCV002135790	uncertain significance	Neuronal ceroid lipofuscinosis	2024-02-24	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 205 of the CLN5 protein (p.Pro205Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21447811, 21990111). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 56541). 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 CLN5 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV000049954	SCV003832398	uncertain significance	Neuronal ceroid lipofuscinosis 5	2022-06-29	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000049954	SCV004808206	uncertain significance	Neuronal ceroid lipofuscinosis 5	2024-03-29	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049954	SCV000082363	probable-pathogenic	Neuronal ceroid lipofuscinosis 5		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.