ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.956_959del (p.Lys319fs) (rs386833967)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632714 SCV000753900 pathogenic Neuronal ceroid lipofuscinosis 2018-03-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CLN5 gene (p.Lys368Serfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acids of the CLN5 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous, or in combination with a second pathogenic CLN5 variant, in several individuals affected with neuronal ceroid liopfuscinosis (PMID: 22532218, 20157158, 20960652, 25976102, Invitae). ClinVar contains an entry for this variant (Variation ID: 56529). This variant has also been reported as c.1002_1006delAACA. Experimental studies are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000632714 SCV001363639 pathogenic Neuronal ceroid lipofuscinosis 2019-11-01 criteria provided, single submitter clinical testing Variant summary: CLN5 c.1103_1106delAACA (p.Lys368SerfsX15) 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. The variant was absent in 243956 control chromosomes (gnomAD). c.1103_1106delAACA has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (e.g. Kohan_2015, Ren_2019, Xin_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049942 SCV000082351 probable-pathogenic Neuronal ceroid lipofuscinosis 5 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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