Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic 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. |