ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1772A>G (p.Tyr591Cys)

gnomAD frequency: 0.00001  dbSNP: rs72555371
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673090 SCV000798258 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-03-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003764505 SCV004604252 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 591 of the GLB1 protein (p.Tyr591Cys). This variant is present in population databases (rs72555371, gnomAD 0.003%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 10737981). ClinVar contains an entry for this variant (Variation ID: 948). 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.Tyr591 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10737981). 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 RCV000000998 SCV000021148 pathogenic GM1-gangliosidosis, type I, with cardiac involvement 2000-01-01 no assertion criteria provided literature only

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