Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384761 | SCV001584406 | pathogenic | GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11 | 2024-09-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr382Serfs*30) 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 present in population databases (rs63750805, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with frontotemporal dementia (PMID: 16862116, 25943890). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98170). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000084473 | SCV002024922 | pathogenic | not provided | 2019-05-02 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004786364 | SCV005400022 | pathogenic | GRN-related frontotemporal lobar degeneration with Tdp43 inclusions | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with frontotemporal lobar degeneration with ubiquitin-positive inclusions (MIM#607485). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with frontotemporal dementia and primary progressive aphasia (PMID: 16862116, PMID: 30599136). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| VIB Department of Molecular Genetics, |
RCV000084473 | SCV000116609 | not provided | not provided | no assertion provided | not provided |