Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV002249057 | SCV002516354 | likely pathogenic | Infantile GM1 gangliosidosis | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003094010 | SCV003231890 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2022-09-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1685330). Disruption of this splice site has been observed in individual(s) with GM1-gangliosidosis (PMID: 27679996). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 5 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). |