Submissions for variant NM_006493.4(CLN5):c.377T>G (p.Leu126Ter)

dbSNP: rs386833972

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000049949	SCV000220699	likely pathogenic	Neuronal ceroid lipofuscinosis 5	2014-09-16	criteria provided, single submitter	literature only
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000049949	SCV000588366	pathogenic	Neuronal ceroid lipofuscinosis 5	2017-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000049949	SCV001977477	pathogenic	Neuronal ceroid lipofuscinosis 5	2021-08-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265586	SCV002548415	likely pathogenic	Neuronal ceroid lipofuscinosis	2022-05-25	criteria provided, single submitter	clinical testing	Variant summary: CLN5 c.524T>G (p.Leu175X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251486 control chromosomes (gnomAD). c.524T>G has been reported in the literature in at least one homozygous individual affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease, Kousi_2012). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae	RCV002265586	SCV003509857	pathogenic	Neuronal ceroid lipofuscinosis	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu175*) in the CLN5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN5 are known to be pathogenic (PMID: 20157158). This variant is present in population databases (rs386833972, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21990111). ClinVar contains an entry for this variant (Variation ID: 56536). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049949	SCV000082358	probable-pathogenic	Neuronal ceroid lipofuscinosis 5		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.