ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.785G>T (p.Gly262Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002651651 SCV003525099 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2021-12-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 262 of the GLB1 protein (p.Gly262Val). For these reasons, this variant has been classified as Pathogenic. 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 missense change has been observed in individual(s) with GM1 gangliosidosis (PMID: 22675082, 26646981). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency).

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