Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Concord Molecular Medicine Laboratory, |
RCV002512431 | SCV002820074 | likely pathogenic | GRN-related frontotemporal lobar degeneration with Tdp43 inclusions | 2023-01-16 | criteria provided, single submitter | clinical testing | This single nucleotide insertion has been detected in a patient with primary progressive aphasia and weakness. MRI brain was consistent with frontotemporal dementia, and EMG was consistent with motor neuron disease. This insertion has not been observed in control population database (gnomAD). The insertion results in a premature stop codon, p.(Gly168Valfs*30) that is predicted to be subject to nonsense mediated decay. Haploinsufficiency of GRN is a well established mechanism of disease for autosomal dominant frontotemporal lobar degeneration with ubiquitin-positive inclusions (OMIM#607485). The current evidence allows a classification of likely pathogenic (ACMG criteria: PVS1, PM2_supporting). |