ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.214C>T (p.Gln72Ter) (rs386833709)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812617 SCV000952936 pathogenic Neuronal ceroid lipofuscinosis 2018-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln72*) 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 heterozygosis in an individual affected with neuronal ceroid lipofuscinosis (PMID: 21990111). ClinVar contains an entry for this variant (Variation ID: 56258). Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000049670 SCV001361078 likely pathogenic Juvenile neuronal ceroid lipofuscinosis 2019-09-27 criteria provided, single submitter clinical testing Variant summary: CLN3 c.214C>T (p.Gln72X) 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 was absent in 249072 control chromosomes (gnomAD). c.214C>T has been reported in the literature in an individual affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease), however, limited available information was provided (Kousi_2011). These data therefore do not allow clear conclusions about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites 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) RCV000049670 SCV000082077 probable-pathogenic Juvenile neuronal ceroid lipofuscinosis no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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