ClinVar Miner

Submissions for variant NM_001042432.2(CLN3):c.240del (p.Pro81fs)

dbSNP: rs748710466
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255009 SCV000322209 likely pathogenic not provided 2023-01-03 criteria provided, single submitter clinical testing Reported previously in association with juvenile neuronal ceroid lipofuscinosis (JNCL), and functional analysis showed decreased mRNA expression due to truncation of the CLN3 protein in cells with this variant as compared to normal controls (Adams et al., 2010; Kwon et al., 2011; Miller et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23539563, 22013180, 20187884)
Genome-Nilou Lab RCV001729499 SCV001977449 pathogenic Neuronal ceroid lipofuscinosis 3 2021-08-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282095 SCV002572428 likely pathogenic Neuronal ceroid lipofuscinosis 2022-08-30 criteria provided, single submitter clinical testing Variant summary: CLN3 c.240delG (p.Pro81ArgfsX100) 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 251492 control chromosomes (gnomAD). c.240delG has been reported in the literature in at-least one individual affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease) (examples: Adams_2010, Kwon_2011 and Miller_2013). Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.