ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.424del (p.Val142fs) (rs386833720)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049681 SCV000485325 pathogenic Juvenile neuronal ceroid lipofuscinosis 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000819681 SCV000960355 pathogenic Neuronal ceroid lipofuscinosis 2019-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val142Leufs*39) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) (PMID: 20187884, 17947292, 9311735). ClinVar contains an entry for this variant (Variation ID: 56269). Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000819681 SCV001372283 pathogenic Neuronal ceroid lipofuscinosis 2020-06-01 criteria provided, single submitter clinical testing Variant summary: CLN3 c.424delG (p.Val142LeufsX39) 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 4e-06 in 251294 control chromosomes (gnomAD). c.424delG has been reported in the literature in the compound heterozygous or homozygous state in multiple individuals affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease) (e.g. Kousi_2012, Munroe_1997). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters (evaluation after 2014) cite 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) RCV000049681 SCV000082088 probable-pathogenic Juvenile neuronal ceroid lipofuscinosis no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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