ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.105G>A (p.Trp35Ter) (rs386833700)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760369 SCV000890232 pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing The W35X variant in the CLN3 gene has been reported previously in association with neuronal ceroid lipofuscinosis (Kousi et al., 2012; Kwon et al., 2011; Miller et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay, of which nonsense-mediated mRNA decay has been supported in a study of lymphoblast cells from an affected individual (Miller et al., 2013). The W35X variant is not observed at a significance frequency in large population cohorts (Lek et al., 2016). We interpret W35X as a pathogenic variant.
Invitae RCV001217036 SCV001388863 pathogenic Neuronal ceroid lipofuscinosis 2019-03-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp35*) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs386833700, ExAC 0.006%). This variant has been observed in several individuals affected with Batten disease (PMID: 21990111, 22013180, 23539563). ClinVar contains an entry for this variant (Variation ID: 56249). Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049661 SCV000082068 probable-pathogenic Juvenile neuronal ceroid lipofuscinosis no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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