ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1144-2A>G (rs1553607014)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673337 SCV000798526 likely pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-03-13 criteria provided, single submitter clinical testing
Invitae RCV001071947 SCV001237283 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 11 of the GLB1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with GM1 gangliosidosis (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 557226). 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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