ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.451G>A (p.Asp151Asn)

gnomAD frequency: 0.00002  dbSNP: rs375582374
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001973484 SCV002266608 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 151 of the GLB1 protein (p.Asp151Asn). This variant is present in population databases (rs375582374, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1474580). 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 GLB1 protein function. This variant disrupts the p.Asp151 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15365997, 15791924, 32219518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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