Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Clinical and Movement Neurosciences, |
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. |