Submissions for variant NM_002087.4(GRN):c.1179+3A>G

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003781416	SCV004573395	pathogenic	GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11	2024-11-26	criteria provided, single submitter	clinical testing	This sequence change falls in intron 10 of the GRN gene. It does not directly change the encoded amino acid sequence of the GRN protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with behavioral variant of frontotemporal dementia, corticobasal syndrome or nonfluent primary progressive aphasia (PMID: 29525180, 32507413). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2927226). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in retention of intron 10, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 32507413). For these reasons, this variant has been classified as Pathogenic.