ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.397-1G>A

gnomAD frequency: 0.00001  dbSNP: rs398123353
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178086 SCV000230081 pathogenic not provided 2012-11-01 criteria provided, single submitter clinical testing
Counsyl RCV000667741 SCV000792240 likely pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-06-13 criteria provided, single submitter clinical testing
Invitae RCV001211514 SCV001383057 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-11-04 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 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 (rs398123353, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with GM1-gangliosidosis (PMID: 25936995). ClinVar contains an entry for this variant (Variation ID: 92906). 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 RCV000178086 SCV002038988 pathogenic not provided 2021-12-20 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 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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