ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.1319G>A (p.Arg440Gln)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003589323 SCV004306599 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2024-08-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 440 of the TBK1 protein (p.Arg440Gln). This variant is present in population databases (rs773161577, gnomAD 0.003%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 33618928; Invitae). 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 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.
PreventionGenetics, part of Exact Sciences RCV003892224 SCV004716817 uncertain significance TBK1-related disorder 2023-11-06 no assertion criteria provided clinical testing The TBK1 c.1319G>A variant is predicted to result in the amino acid substitution p.Arg440Gln. This variant was reported in an individual with amyotrophic lateral sclerosis (Nunes Gonçalves et al. 2021. PubMed ID: 33618928). This variant is reported in 0.0028% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-64879776-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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