ClinVar Miner

Submissions for variant NM_007126.5(VCP):c.464G>C (p.Arg155Pro)

dbSNP: rs121909329
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001387337 SCV001587941 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia 2022-09-27 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects VCP function (PMID: 19506019, 20604808, 26549226). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg155 amino acid residue in VCP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15034582, 17763460, 19364651). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 8472). This missense change has been observed in individuals with Inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (PMID: 15034582, 28692196). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 155 of the VCP protein (p.Arg155Pro).
Revvity Omics, Revvity RCV003137504 SCV003820389 uncertain significance not provided 2019-04-24 criteria provided, single submitter clinical testing
OMIM RCV000008993 SCV000029207 pathogenic Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 2004-04-01 no assertion criteria provided literature only

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