ClinVar Miner

Submissions for variant NM_018941.3(CLN8):c.562_563delCT (rs386834132)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000050126 SCV000220700 likely pathogenic Neuronal ceroid lipofuscinosis 8 2014-09-16 criteria provided, single submitter literature only
Invitae RCV001385516 SCV001585397 pathogenic Neuronal ceroid lipofuscinosis 2020-09-17 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CLN8 gene (p.Leu188Valfs*58). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acids of the CLN8 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 22220808). This variant disrupts the C-terminus of the CLN8 protein. Other variant(s) that disrupt this region (p.Val236Serfs*8) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000050126 SCV001623276 likely pathogenic Neuronal ceroid lipofuscinosis 8 2021-05-14 criteria provided, single submitter clinical testing Variant summary: CLN8 c.562_563delCT (p.Leu188ValfsX58) results in a premature termination codon located in the last exon therefore it is not expected to elicit nonsense mediated decay, but is predicted to cause a truncation of the encoded protein. Truncations downstream of this position have been reported in affected individuals (HGMD). The variant allele was found at a frequency of 4e-06 in 250252 control chromosomes (gnomAD). The variant, c.562_563delCT, or the equivalent protein level change (p.Leu188Valfs), has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis, CLN8-Related (Allen_2012, Lee_2014). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050126 SCV000082536 probable-pathogenic Neuronal ceroid lipofuscinosis 8 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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