ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.427C>T (p.Arg143Cys)

dbSNP: rs1027249002
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995896 SCV001150287 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2019-06-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000995896 SCV003515515 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2022-04-26 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects TBK1 function (PMID: 28008748). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 807706). This missense change has been observed in individual(s) with clinical features of TBK1-related conditions (PMID: 26476236, 28008748). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 143 of the TBK1 protein (p.Arg143Cys).

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