ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.936del (p.Phe312fs) (rs386833966)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803462 SCV000943334 pathogenic Neuronal ceroid lipofuscinosis 2018-12-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CLN5 gene (p.Phe361Leufs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acids of the CLN5 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with neuronal ceroid lipofuscinosis (NCL) (PMID: 20157158). ClinVar contains an entry for this variant (Variation ID: 56528). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the CLN5 protein. Other variant(s) that disrupt this region (p.Tyr392*) have been observed in individuals with CLN5-related conditions (PMID: 9662406, 20052765, 11971870, 24058541, 24038957). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000803462 SCV001338973 likely pathogenic Neuronal ceroid lipofuscinosis 2020-03-23 criteria provided, single submitter clinical testing Variant summary: CLN5 c.1083delT (p.Phe361LeufsX4) 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 1.2e-05 in 246982 control chromosomes. c.1083delT has been reported in the literature in an individual affected with Neuronal Ceroid-Lipofuscinosis (Xin_2010). 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. One laboratory 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) RCV000049941 SCV000082350 probable-pathogenic Neuronal ceroid lipofuscinosis 5 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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