Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000174679 | SCV000226022 | pathogenic | not provided | 2014-03-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586055 | SCV000696685 | pathogenic | GM1 gangliosidosis | 2016-08-09 | criteria provided, single submitter | clinical testing | Variant summary: The GLB1 c.1445G>A (p.Arg482His) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/120872 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GLB1 variant (0.0020412). This variant has been reported in multiple patients with Morquio B disease and Gm1-gangliosidosis. Functional testing showed that variant allele with non-detectable enzyme activity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
| Invitae | RCV001034863 | SCV001198163 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 482 of the GLB1 protein (p.Arg482His). This variant is present in population databases (rs72555391, gnomAD 0.006%). This missense change has been observed in individual(s) with GLB1-related conditions (PMID: 1928092, 15943552). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 932). 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: 15943552). For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV000000981 | SCV002767855 | pathogenic | Infantile GM1 gangliosidosis | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Type I GM1-gangliosidosis (MIM#230500). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to histidine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 3 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (2 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ß domain 1 (PMID: 25936995). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. At least 10 type I GM1-gangliosidosis (MIM#230500) patients have been reported to be either homozygous or compound heterozygous for this variant (ClinVar; PMID: 10737981, 15943552, 15714521, 17221873, 25936995). (SP) 1201 - Heterozygous variant detected in trans with a second pathogenic heterozygous variant (NM_000404.3:c.1480-2A>G) in a recessive disease. (SP) 1206 - This variant has been shown to be paternally inherited (SA pathology Lab ID: FAMCa 2473751)/ (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV002476905 | SCV002787745 | pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2021-12-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000174679 | SCV003840641 | pathogenic | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant results in almost no residual enzymatic activity (Caciotti et al., 2005); This variant is associated with the following publications: (PMID: 15714521, 15943552, 7586649, 1487238, 11511921, 1928092, 16538002, 25936995, 22128166, 8500799, 21520340, 18353697, 15365997, 17221873, 21497194, 10737981, 34426522, 32779865) |
| OMIM | RCV000119099 | SCV000021130 | pathogenic | Mucopolysaccharidosis, MPS-IV-B | 1993-05-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000000981 | SCV000021131 | pathogenic | Infantile GM1 gangliosidosis | 1993-05-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000119099 | SCV000797872 | pathogenic | Mucopolysaccharidosis, MPS-IV-B | 2018-02-13 | no assertion criteria provided | clinical testing |