ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.146G>A (p.Arg49His)

gnomAD frequency: 0.00002  dbSNP: rs780523881
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624583 SCV000742823 likely pathogenic Inborn genetic diseases 2019-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001057694 SCV001222198 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 49 of the GLB1 protein (p.Arg49His). This variant is present in population databases (rs780523881, gnomAD 0.01%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 15986423, 30267299). ClinVar contains an entry for this variant (Variation ID: 521991). 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. Experimental studies have shown that this missense change affects GLB1 function (PMID: 20175788).
GeneDx RCV003238787 SCV003936369 pathogenic not provided 2023-06-29 criteria provided, single submitter clinical testing Published functional studies demonstrate a significant reduction in enzyme activity compared to wildtype (Hofer et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20175788, 30267299, 15986423)
Counsyl RCV000672724 SCV000797858 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-02-13 flagged submission clinical testing

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