ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.522dup (p.Trp175fs) (rs386833979)

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
Counsyl RCV000049956 SCV000486348 likely pathogenic Neuronal ceroid lipofuscinosis 5 2016-05-16 criteria provided, single submitter clinical testing
Invitae RCV000690321 SCV000818003 pathogenic Neuronal ceroid lipofuscinosis 2019-05-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CLN5 gene (p.Trp224Leufs*30). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acids of the CLN5 protein. This variant is present in population databases (rs770949806, ExAC 0.01%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant (p.Trp75X) in individuals affected with neuronal ceroid lipofuscinosis (PMID: 21990111, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as c.669insC and p.E253X in the literature. ClinVar contains an entry for this variant (Variation ID: 56543). Experimental studies have shown that this change results in an unstable polypeptide and disrupts lysosomal trafficking of the CLN5 protein (PMID: 20052765). A different truncation (p.Lys368Serfs*15) that lies downstream of this variant has been determined to be pathogenic (PMID: 22532218, 20157158, 20960652, 25976102, Invitae). This suggests that deletion of this region of the CLN5 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049956 SCV000082365 probable-pathogenic Neuronal ceroid lipofuscinosis 5 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.