ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.397-1G>A (rs398123353)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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 2019-10-11 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 and likely results in an absent or disrupted protein product. This variant is present in population databases (rs398123353, ExAC 0.02%). Disruption of this splice site has been observed in an individual affected 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, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GLB1 are known to be pathogenic (PMID: 18524657). For these reasons, this variant has been classified as Pathogenic.

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