ClinVar Miner

Submissions for variant NM_007126.5(VCP):c.478G>C (p.Ala160Pro)

dbSNP: rs1554668805
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000639654 SCV000761234 pathogenic Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 160 of the VCP protein (p.Ala160Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of VCP-related conditions and/or inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (PMID: 28692196, 29754758; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 532761). 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 with a negative predictive value of 80%. This variant disrupts the p.Ala160 amino acid residue in VCP. Other variant(s) that disrupt this residue have been observed in individuals with VCP-related conditions (PMID: 36980948), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000993545 SCV001146627 uncertain significance not provided 2018-11-26 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000993545 SCV001248046 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535609 SCV001749626 not provided Inclusion body myopathy with Paget disease of bone and frontotemporal dementia no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 11-27-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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