Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003089263 | SCV003466223 | uncertain significance | Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 133 of the VCP protein (p.Val133Leu). This variant is present in population databases (rs775567003, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with VCP-related conditions. ClinVar contains an entry for this variant (Variation ID: 2154906). 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 VCP 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. |
Undiagnosed Diseases Network, |
RCV004763532 | SCV005368719 | uncertain significance | Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 | 2024-04-03 | no assertion criteria provided | clinical testing |