ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1009C>G (p.Leu337Val)

dbSNP: rs376034559
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001986227 SCV002279228 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2021-10-09 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. This variant disrupts the p.Leu337 amino acid residue in GLB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23151865, 25936995). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GLB1 protein function. This variant has not been reported in the literature in individuals affected with GLB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 337 of the GLB1 protein (p.Leu337Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine.

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