ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.631C>T (p.Gln211Ter) (rs386833737)

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
Integrated Genetics/Laboratory Corporation of America RCV000049700 SCV001361076 likely pathogenic Juvenile neuronal ceroid lipofuscinosis 2019-03-15 criteria provided, single submitter clinical testing Variant summary: CLN3 c.631C>T (p.Gln211X) 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 (e.g. c.944dupA (p.His315fsX67)). The variant allele was found at a frequency of 4.1e-06 in 243782 control chromosomes (gnomAD). c.631C>T has been reported in the literature in an individual affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease) (Munroe 1997, Kwon 2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001239013 SCV001411858 pathogenic Neuronal ceroid lipofuscinosis 2019-11-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln211*) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs386833737, ExAC 0.002%). This variant has been observed in an individual with clinical features of neuronal ceroid lipofuscinosis (PMID: 22013180). ClinVar contains an entry for this variant (Variation ID: 56288). Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049700 SCV000082107 probable-pathogenic Juvenile neuronal ceroid lipofuscinosis no assertion criteria provided not provided Converted during submission to 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.