ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.902C>T (p.Ala301Val) (rs750531880)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670128 SCV000794945 likely pathogenic GM1 gangliosidosis type 2; Gangliosidosis GM1 type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-10-23 criteria provided, single submitter clinical testing
GeneDx RCV000418628 SCV000520957 pathogenic not provided 2017-02-02 criteria provided, single submitter clinical testing The c.902 C>T pathogenic variant in the GLB1 gene has been reported previously with another GLB1 variant in multiple unrelated individuals with GM1-gangliosidosis (Santamaria et al., 2006; Yang et al., 2010; Hofer et al., 2010). Functional studies have shown that the c.902 C>T variant is associated with significantly reduced beta-galactosidase activity (Yang et al., 2010). The c.902 C>T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.902 C>T may create a cryptic splice donor site in exon 8, which may cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.902 C>T change in this individual is unknown. If c.902 C>T does not alter splicing, it will result in the A301V missense change. The A301V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.902 C>T as a pathogenic variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.