ClinVar Miner

Submissions for variant NM_002087.4(GRN):c.1477C>T (p.Arg493Ter) (rs63751294)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000084491 SCV000322383 pathogenic not provided 2018-11-26 criteria provided, single submitter clinical testing The R493X variant in the GRN gene is one of the most common variants reported in the GRN gene in individuals with frontotemporal dementia (Gass et al., 2006; Huey et al., 2006; Rademakers et al., 2007). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R493X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R493X as a pathogenic variant.
Athena Diagnostics Inc RCV000084491 SCV000843034 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing
Invitae RCV001039647 SCV001203184 pathogenic Grn-related frontotemporal lobar degeneration with Tdp43 inclusions; Ceroid lipofuscinosis, neuronal, 11 2019-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg493*) in the GRN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with frontotemporal dementia and primary progressive aphasia (PMID: 16950801, 30279455, 26791154). This variant has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16014). Loss-of-function variants in GRN are known to be pathogenic (PMID: 22608501). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000017387 SCV000037659 pathogenic Grn-related frontotemporal lobar degeneration with Tdp43 inclusions 2011-04-01 no assertion criteria provided literature only
GeneReviews RCV000017387 SCV000040894 pathogenic Grn-related frontotemporal lobar degeneration with Tdp43 inclusions 2020-02-03 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084491 SCV000116627 not provided not provided no assertion provided not provided

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