ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.396+2T>C

dbSNP: rs1057517738
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414347 SCV000490539 pathogenic not provided 2015-04-28 criteria provided, single submitter clinical testing The c.396+2 T>C splice site variant in the GLB1 gene destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense -mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this variant has not been previously reported to our knowledge, it is expected to be pathogenic.
Invitae RCV003766144 SCV004595880 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-01-20 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 372370). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor 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).

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