ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.734-8A>G

gnomAD frequency: 0.00001  dbSNP: rs398123357
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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) RCV000078720 SCV000110580 uncertain significance not provided 2014-05-19 criteria provided, single submitter clinical testing
Counsyl RCV000669168 SCV000793890 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-09-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317082 SCV004020601 uncertain significance not specified 2023-06-29 criteria provided, single submitter clinical testing Variant summary: GLB1 c.734-8A>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a 3' acceptor site. Two predict the variant weakens a 3' acceptor site. Four predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 249454 control chromosomes. c.734-8A>G has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVB (Morquio Syndrome B) and Gangliosidosis (Uttarilli_2019, Hofer_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35614200, 20175788, 30408610). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
GenomeConnect - GM1 RCV002508193 SCV002818103 not provided GM1 gangliosidosis no assertion provided phenotyping only Variant classified as Likely pathogenic and reported on 12-08-2021 by Lab or GTR ID 500188. GenomeConnect-GM1 assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.

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