ClinVar Miner

Submissions for variant NM_002087.3(GRN):c.102del (p.Gly35fs) (rs63751073)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000084427 SCV001167862 pathogenic not provided 2019-02-08 criteria provided, single submitter clinical testing The c.102delC variant in the GRN gene has been reported previously in association with frontotemporal lobar degeneration (Gass et al., 2006; Rusina et al., 2011). The deletion causes a frameshift starting with codon Glycine 35, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 19 of the new reading frame, denoted p.Gly35GlufsX19. Functional studies suggest that the c.102delC variant causes loss of normal protein function through nonsense-mediated mRNA decay (Skoglund et al., 2008). The c.102delC variant is not observed in large population cohorts (Lek et al., 2016). Therefore, we interpret this variant as pathogenic.
Invitae RCV001241659 SCV001414690 pathogenic Grn-related frontotemporal lobar degeneration with Tdp43 inclusions; Ceroid lipofuscinosis, neuronal, 11 2019-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly35Glufs*19) 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 individuals affected with frontotemporal lobar degeneration (PMID: 16950801, 21569259). ClinVar contains an entry for this variant (Variation ID: 98125). Loss-of-function variants in GRN are known to be pathogenic (PMID: 22608501). For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084427 SCV000116563 not provided not provided no assertion provided not provided

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