Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815880 | SCV000956358 | uncertain significance | GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 212 of the GRN protein (p.Arg212Gln). This variant is present in population databases (rs63750787, gnomAD 0.03%). This missense change has been observed in individual(s) with frontotemporal dementia (PMID: 21800185). ClinVar contains an entry for this variant (Variation ID: 98145). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GRN protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002513901 | SCV003646399 | uncertain significance | Inborn genetic diseases | 2021-04-20 | criteria provided, single submitter | clinical testing | Unlikely to be causative of GRN-related frontotemporal dementia (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
VIB Department of Molecular Genetics, |
RCV000084448 | SCV000116584 | not provided | not provided | no assertion provided | not provided |