ClinVar Miner

Submissions for variant NM_013254.4(TBK1):c.992+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1341055534
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Total submissions: 4
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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 RCV000995897 SCV001150288 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2018-01-08 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196463 SCV001367071 pathogenic Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8 2018-10-26 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PP3,PP5.
Labcorp Genetics (formerly Invitae), Labcorp RCV000995897 SCV002240071 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 2023-06-26 criteria provided, single submitter clinical testing The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in exon 8 skipping and introduces a premature termination codon (PMID: 31244341). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 807707). Disruption of this splice site has been observed in individuals with amyotrophic lateral sclerosis (PMID: 30033073, 31244341). It has also been observed to segregate with disease in related individuals. This sequence change affects a donor splice site in intron 8 of the TBK1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003333118 SCV004040635 pathogenic Amyotrophic lateral sclerosis 2023-10-05 criteria provided, single submitter clinical testing

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