ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.2107G>T (p.Glu703Ter)

dbSNP: rs1565825132
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London RCV000768401 SCV000886403 likely pathogenic Primary progressive non fluent aphasia; Corticobasal syndrome no assertion criteria provided research The Glu703* variant in the TBK1 gene was found in an affected member of a family with autosomal dominant ALS/FTD. The affected family member developed progressive non-fluent aphasia-corticobasal syndrome overlap. The brain pathology showed TDP-43, which has been previously associated with TBK1 mutations (Freischmidt et al., 2015; Pottier et al., 2015; Van Mossevelde et al., 2016). This variant was absent from 138,000 unrelated exome and genome sequences from the gnomAD database. This variant is predicted to result in a truncated protein product with loss of the highly conserved adaptor binding site at the C-terminal coiled-coil domain 2, which likely impacts complex formation (Goncalves et al., 2011; Freischmidt et al., 2015). In silico predictive algorithms predict this variant to be deleterious.

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