Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV005179733 | SCV005815721 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu695Argfs*16) in the TBK1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the TBK1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of TBK1-related conditions (PMID: 30293248). This variant disrupts a region of the TBK1 protein in which other variant(s) (p.Gly722Asp) have been observed in individuals with TBK1-related conditions (internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |