ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1769G>A (p.Arg590His) (rs398123351)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174999 SCV000226418 pathogenic not provided 2013-11-06 criteria provided, single submitter clinical testing
Counsyl RCV000674722 SCV000800111 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-05-22 criteria provided, single submitter clinical testing
Invitae RCV000794211 SCV000933605 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 590 of the GLB1 protein (p.Arg590His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs398123351, ExAC 0.002%). This variant has been observed in individuals affected with GM1-gangliosidosis (PMID: 8213816, 26646981). ClinVar contains an entry for this variant (Variation ID: 92901). Experimental studies have shown that this missense change disrupts -galactosidase activity (PMID: 8213816, 23337983). Variants that disrupt the p.Arg590 amino acid residue in GLB1 have been observed in affected individuals (PMID: 16941474, 23430803, 17309651, 17664528). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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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