ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.1718G>A (p.Arg573His)

gnomAD frequency: 0.00005  dbSNP: rs186475789
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538483 SCV000656242 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2024-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 573 of the TBK1 protein (p.Arg573His). This variant is present in population databases (rs186475789, gnomAD 0.01%). This variant has been reported in the amyotrophic lateral sclerosis variant database (PMID: 25700176, www.alsdb.org). ClinVar contains an entry for this variant (Variation ID: 475936). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg573 amino acid residue in TBK1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28365590). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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.

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