ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1471G>A (p.Asp491Asn)

gnomAD frequency: 0.00001  dbSNP: rs780232995
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674513 SCV000799860 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-05-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001868281 SCV002134773 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-12-25 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 491 of the GLB1 protein (p.Asp491Asn). This variant is present in population databases (rs780232995, gnomAD 0.006%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 10338095, 33737400). This variant is also known as c.1521G>A. ClinVar contains an entry for this variant (Variation ID: 558272). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GLB1 function (PMID: 23337983). This variant disrupts the p.Asp491 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been observed in individuals with GLB1-related conditions (PMID: 17309651, 31761138), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV002289953 SCV002579114 uncertain significance Mucopolysaccharidosis, MPS-IV-B 2022-04-14 criteria provided, single submitter clinical testing

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