ClinVar Miner

Submissions for variant NM_007126.5(VCP):c.383G>C (p.Gly128Ala)

dbSNP: rs1554668979
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498690 SCV000590020 uncertain significance not provided 2024-07-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28692196, 29754758, 31914217)
Labcorp Genetics (formerly Invitae), Labcorp RCV003766796 SCV004569724 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 128 of the VCP protein (p.Gly128Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of VCP-related conditions (PMID: 28692196). ClinVar contains an entry for this variant (Variation ID: 432305). 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. This variant disrupts the p.Gly128 amino acid residue in VCP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28692196, 29754758, 30103957, 31914217). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000498690 SCV005413889 likely pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing PP2, PP3, PM2_moderate, PS4_moderate

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