Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001897200 | SCV002157241 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 601 of the TBK1 protein (p.Phe601Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TBK1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TBK1 protein function. 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. |
| Prevention |
RCV004746480 | SCV005364558 | uncertain significance | TBK1-related disorder | 2024-09-25 | no assertion criteria provided | clinical testing | The TBK1 c.1803T>G variant is predicted to result in the amino acid substitution p.Phe601Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |