Submissions for variant NM_002087.4(GRN):c.1252C>T (p.Arg418Ter)

dbSNP: rs63751180

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000084480	SCV000613572	pathogenic	not provided	2015-08-07	criteria provided, single submitter	clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000995559	SCV001149796	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions	2019-06-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000084480	SCV001250433	pathogenic	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001390599	SCV001592386	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11	2024-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg418*) in the GRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRN are known to be pathogenic (PMID: 16862116, 16950801, 22608501). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with frontotemporal dementia (PMID: 16862116). ClinVar contains an entry for this variant (Variation ID: 98177). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000995559	SCV002757807	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions	2022-12-01	criteria provided, single submitter	clinical testing
Human Genetics Bochum, Ruhr University Bochum	RCV002463638	SCV002758562	pathogenic	Amyotrophic lateral sclerosis type 10	2022-10-04	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PVS1, PM2
GeneDx	RCV000084480	SCV005202129	pathogenic	not provided	2023-12-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay (NMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34697415, 25525159, 21813674, 23475817, 24993774, 19125255, 19649643, 22608501, 16950801, 32178712, 31707213, 28473694, 28453791, 23742080, 24163244, 23117491, 21482928, 21047645, 31914217, 17698705, 16862116, 22895706, 19204154, 35790423)
VIB Department of Molecular Genetics, University of Antwerp	RCV000084480	SCV000116616	not provided	not provided		no assertion provided	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000084480	SCV001809013	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000084480	SCV001958902	likely pathogenic	not provided		no assertion criteria provided	clinical testing