ClinVar Miner

Submissions for variant NM_000100.3(CSTB):c.202C>T (p.Arg68Ter) (rs74315442)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000008904 SCV000436264 pathogenic Unverricht-Lundborg syndrome 2016-06-14 criteria provided, single submitter clinical testing The c.202C>T (p.Arg68Ter) variant has been reported in at least five studies in which it is found in a total of 11 Unverricht-Lundborg disease patients, including two affected siblings in a homozygous state, seven patients in a compound heterozygous state (including two sibling pairs), and in two patient alleles where zygosity was not specified (Pennacchio et al. 1996; Lafrenière et al. 1997; de Haan et al. 2004; Koskenkorva et al. 2010; Mancini et al. 2016). The p.Arg68Ter variant was absent from 377 controls but is reported at a frequency of 0.00006 in the European (Non-Finnish) population of the Exome Aggregation Consortium. Functional analyses demonstrated that the variant resulted in reduced cell viability by 26% compared to wild-type in transfected CHO-K1 cells (Ceru et al. 2010). Additionally, the p.Arg68Ter variant protein did not localize to the nucleus. The variant produced an unfolded protein leading to protein aggregation which resulted in perinuclear aggregates that were more pronounced than wild type (Rabzelj et al. 2005; Ceru et al. 2010; Polajnar et al. 2012). Based on the evidence and the potential impact of stop-gained variants, the p.Arg68Ter variant is classified as pathogenic for Unverricht-Lundborg disease.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626611 SCV000747312 pathogenic Dystonia; Motor delay; Aplasia/Hypoplasia of the corpus callosum; Dyskinesia; Progressive microcephaly; Global brain atrophy; Intellectual disability, severe; Severe global developmental delay 2017-01-01 criteria provided, single submitter clinical testing
OMIM RCV000008904 SCV000029114 pathogenic Unverricht-Lundborg syndrome 2005-02-01 no assertion criteria provided literature only
GeneReviews RCV000008904 SCV000195832 pathogenic Unverricht-Lundborg syndrome 2014-11-25 no assertion criteria provided literature only
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000656065 SCV000588341 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15

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