Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001853259 | SCV002238392 | pathogenic | Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia | 2022-08-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects VCP function (PMID: 27226613). 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 expected to disrupt VCP protein function. ClinVar contains an entry for this variant (Variation ID: 218306). This missense change has been observed in individuals with clinical features of inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD) (PMID: 23000505, 25878907, 29127544). It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 97 of the VCP protein (p.Gly97Glu). |
OMIM | RCV000202492 | SCV000257498 | pathogenic | Charcot-Marie-Tooth disease type 2Y | 2015-01-01 | no assertion criteria provided | literature only |