Submissions for variant NM_002087.4(GRN):c.328C>T (p.Arg110Ter)

dbSNP: rs63750411

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000084436	SCV000779672	pathogenic	not provided	2022-02-21	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also reported in an individual with a clinical diagnosis of posterior cortical atrophy with visual deficits, apperceptive visual agnosia, and occipital cortical atrophy (Caroppo et al., 2015); This variant is associated with the following publications: (PMID: 25525159, 29614680, 17698705, 30528841, 28749476, 30279455, 22312439, 25546130)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000767861	SCV000897721	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions	2021-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000084436	SCV001250430	pathogenic	not provided	2023-10-01	criteria provided, single submitter	clinical testing	GRN: PVS1, PM2
Athena Diagnostics	RCV000084436	SCV001475245	pathogenic	not provided	2020-05-11	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
New York Genome Center	RCV001291777	SCV001480394	pathogenic	Neuronal ceroid lipofuscinosis 11	2020-04-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001387934	SCV001588693	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11	2022-07-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 98134). This premature translational stop signal has been observed in individual(s) with clinical features of frontotemporal dementia (PMID: 17698705, 22312439, 30528841). This variant is present in population databases (rs63750411, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg110*) 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).
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000084436	SCV005198422	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
VIB Department of Molecular Genetics, University of Antwerp	RCV000084436	SCV000116572	not provided	not provided		no assertion provided	not provided