ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.733+1G>A

dbSNP: rs1041204916
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668507 SCV000793123 likely pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-07-28 criteria provided, single submitter clinical testing
Invitae RCV001203710 SCV001374886 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-11-16 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with GM1-gangliosidosis (PMID: 15714521). ClinVar contains an entry for this variant (Variation ID: 553125). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001784254 SCV002032483 pathogenic not provided 2021-12-10 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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