Submissions for variant NM_013254.4(TBK1):c.1760+4_1760+7del

dbSNP: rs753802322

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002547698	SCV003481772	uncertain significance	Frontotemporal dementia and/or amyotrophic lateral sclerosis 4	2022-02-24	criteria provided, single submitter	clinical testing	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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with TBK1-related conditions. This variant is present in population databases (rs753802322, gnomAD 0.005%). This sequence change falls in intron 16 of the TBK1 gene. It does not directly change the encoded amino acid sequence of the TBK1 protein. It affects a nucleotide within the consensus splice site.
CeGaT Center for Human Genetics Tuebingen	RCV004570865	SCV005050604	likely pathogenic	not provided	2024-06-01	criteria provided, single submitter	clinical testing	TBK1: PM2, PP1:Moderate, PP3, PS3:Supporting
Mayo Clinic Laboratories, Mayo Clinic	RCV004570865	SCV005408361	uncertain significance	not provided	2024-01-29	criteria provided, single submitter	clinical testing	PP3
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	RCV001358670	SCV001554459	risk factor	Severe SARS-CoV-2 infection, susceptibility to	2020-10-03	no assertion criteria provided	clinical testing	This variant in homozygous state probably impaires type I interferon immunity and favores a severe disease course of COVID-19.