ClinVar Miner

Submissions for variant NM_018941.3(CLN8):c.499G>T (p.Glu167Ter) (rs144495588)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187127 SCV000240703 pathogenic not provided 2015-12-09 criteria provided, single submitter clinical testing p.Glu167Stop (GAG>TAG): c.499 G>T in exon 2 of the CLN8 gene (NM_018941.3) A E167X nonsense mutation has been identified in the CLN8 gene. The E167X nonsense mutation in the CLN8 gene is predicted to cause loss of normal protein function through protein truncation, as the last 120 residues are lost. Although this mutation has not been reported previously to our knowledge, it is interpreted to be a pathogenic mutation. The finding of a single CLN8 mutation is not sufficient to establish a diagnosis of a CLN8-related disorder. The variant is found in EPILEPSY panel(s).
Genetic Services Laboratory,University of Chicago RCV000503130 SCV000594158 pathogenic Neuronal ceroid lipofuscinosis 2016-07-26 criteria provided, single submitter clinical testing
Invitae RCV000503130 SCV001198328 pathogenic Neuronal ceroid lipofuscinosis 2019-11-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CLN8 gene (p.Glu167*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 120 amino acids of the CLN8 protein. This variant is present in population databases (rs144495588, ExAC 0.005%). This variant has been observed in an individual with a clinical diagnosis of neuronal ceroid lipofuscinosis (PMID: 26075876). ClinVar contains an entry for this variant (Variation ID: 205194). 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 CLN8 protein. Other variant(s) that disrupt this region (Leu188Valfs*58) have been determined to be pathogenic (PMID:22220808). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000665564 SCV000789709 likely pathogenic Neuronal ceroid lipofuscinosis 8 2017-02-14 no assertion criteria provided clinical testing

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