Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | |
Gene |
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, |
RCV000084491 | SCV000116627 | not provided | not provided | no assertion provided | not provided |