Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000179306 | SCV000231535 | pathogenic | not provided | 2013-12-06 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000586182 | SCV000696688 | pathogenic | GM1 gangliosidosis | 2017-05-02 | criteria provided, single submitter | clinical testing | Variant summary: The GLB1 c.622C>T (p.Arg208Cys) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a damaging outcome. This variant was found in 7/120010 control chromosomes at a frequency of 0.0000583, which does not exceed the estimated maximal expected allele frequency of a pathogenic GLB1 variant (0.0020412). Multiple publications have cited the variant in affected individuals as homozygotes and compound heterozygotes, and observed little to no enzymatic activity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Invitae | RCV000633470 | SCV000754699 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2019-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 208 of the GLB1 protein (p.Arg208Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs72555366, ExAC 0.02%). This variant has been reported in many individuals affected with GM1-gangliosidosis (PMID: 8213816, 17309651, 15714521, 10338095). ClinVar contains an entry for this variant (Variation ID: 939). Experimental studies have shown that this missense change causes GLB1 protein to be misfolded and abrogates enzyme function (PMID: 8213816, 23337983, 15714521). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000000988 | SCV000021138 | pathogenic | Infantile GM1 gangliosidosis | 1996-01-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000000988 | SCV001132405 | pathogenic | Infantile GM1 gangliosidosis | 2017-02-03 | no assertion criteria provided | clinical testing | |
Counsyl | RCV000984269 | SCV001132406 | pathogenic | GM1 gangliosidosis type 2 | 2017-02-03 | no assertion criteria provided | clinical testing | |
Counsyl | RCV000984270 | SCV001132407 | pathogenic | GM1 gangliosidosis type 3 | 2017-02-03 | no assertion criteria provided | clinical testing | |
Counsyl | RCV000984271 | SCV001132408 | pathogenic | Mucopolysaccharidosis, MPS-IV-B | 2017-02-03 | no assertion criteria provided | clinical testing |