Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics Munich, |
RCV000995552 | SCV001149787 | pathogenic | GM1 gangliosidosis type 2 | 2019-06-11 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001331204 | SCV001523192 | likely pathogenic | Infantile GM1 gangliosidosis | 2020-05-05 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Labcorp Genetics |
RCV001378118 | SCV001575618 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 239 of the GLB1 protein (p.Thr239Met). This variant is present in population databases (rs746766232, gnomAD 0.003%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 15714521, 19472408). ClinVar contains an entry for this variant (Variation ID: 807421). 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: 15714521). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV002279689 | SCV002567394 | pathogenic | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | Functional analysis found that T239M is associated with significantly reduced enzyme activity (Caciotti et al., 2005); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29396849, 15714521, 19472408, 33737400) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702562 | SCV003922652 | likely pathogenic | GM1 gangliosidosis | 2024-06-18 | criteria provided, single submitter | clinical testing | Variant summary: GLB1 c.716C>T (p.Thr239Met) results in a non-conservative amino acid change located in the Glycoside hydrolase 35, catalytic domain (IPR031330) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249238 control chromosomes. c.716C>T has been reported in the literature in compound heterozygous individuals affected with GM1-gangliosidosis (e.g. Caciotti_2005, Hofer_2009, Tebani_JMG_2022). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (e.g. Caciotti_2005). The following publications have been ascertained in the context of this evaluation (PMID: 15714521, 19472408, 33737400). ClinVar contains an entry for this variant (Variation ID: 807421). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005036266 | SCV005658105 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2024-06-20 | criteria provided, single submitter | clinical testing | |
| Genetics and Genomic Medicine Centre, |
RCV001331204 | SCV005873584 | pathogenic | Infantile GM1 gangliosidosis | 2021-12-06 | criteria provided, single submitter | clinical testing |