Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671128 | SCV000796073 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2017-11-29 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001784268 | SCV002024820 | pathogenic | not provided | 2020-02-25 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001861803 | SCV002269862 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2023-12-07 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 1 of the GLB1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has been observed in individual(s) with GM1-gangliosidosis (PMID: 36265282). ClinVar contains an entry for this variant (Variation ID: 555329). For these reasons, this variant has been classified as Pathogenic. |
| Foundation for Research in Genetics and Endocrinology, |
RCV003155274 | SCV003843882 | pathogenic | Infantile GM1 gangliosidosis | 2021-09-13 | criteria provided, single submitter | clinical testing | A homozygous deletion in exon 1/Intron1 of the GLB1 gene that results in the amino acid deletion fron codon 22 to 26 was detected. The observed variant c.65_75+1 (p.Arg22_Asn26delinsGln) has a minor allele frequency of 0.04% gnomAD databases. The in silico prediction of the variant is damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV003155274 | SCV004047639 | likely pathogenic | Infantile GM1 gangliosidosis | criteria provided, single submitter | clinical testing | The splice site c.65_75+1del variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes and in 0.0004% alleles in heterozygous state in gnomAD. This variant has been reported to the ClinVar database as Likely Pathogenic. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. |