ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.1070G>A (p.Arg357Gln)

gnomAD frequency: 0.00002  dbSNP: rs758357594
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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 RCV002000195 SCV002228958 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2024-08-31 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 357 of the TBK1 protein (p.Arg357Gln). This variant is present in population databases (rs758357594, gnomAD 0.004%). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 25803835, 28822984, 30033073, 31000212). ClinVar contains an entry for this variant (Variation ID: 1453239). 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%. Experimental studies have shown that this missense change affects TBK1 function (PMID: 25803835, 28822984). For these reasons, this variant has been classified as Pathogenic.

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