ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1444C>T (p.Arg482Cys)

gnomAD frequency: 0.00001  dbSNP: rs72555365
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665872 SCV000790064 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-03-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001376852 SCV001574038 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 482 of the GLB1 protein (p.Arg482Cys). This variant is present in population databases (rs72555365, gnomAD 0.01%). This missense change has been observed in individual(s) with GLB1-related conditions (PMID: 7586649). ClinVar contains an entry for this variant (Variation ID: 938). 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: 7586649). This variant disrupts the p.Arg482 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1928092, 15943552). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000119100 SCV000021137 pathogenic Mucopolysaccharidosis, MPS-IV-B 1995-08-01 no assertion criteria provided literature only

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