Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001243865 | SCV001417051 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 | 2024-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 629 of the TBK1 protein (p.Gln629His). This variant is present in population databases (rs752047246, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TBK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 968673). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TBK1 protein function with a negative predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587090 | SCV005076161 | uncertain significance | not specified | 2024-04-15 | criteria provided, single submitter | clinical testing | Variant summary: TBK1 c.1887G>C (p.Gln629His) results in a non-conservative amino acid change located in the TANK-binding kinase 1, coiled-coil domain 1 (IPR041309) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 244366 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1887G>C in individuals affected with Frontotemporal Dementia And/or Amyotrophic Lateral Sclerosis 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 968673). Based on the evidence outlined above, the variant was classified as uncertain significance. |