ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.335A>C (p.His112Pro)

gnomAD frequency: 0.00003  dbSNP: rs753965226
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670769 SCV000795665 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-11-12 criteria provided, single submitter clinical testing
Invitae RCV002531261 SCV003525100 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 112 of the GLB1 protein (p.His112Pro). This variant is present in population databases (rs753965226, gnomAD 0.004%). This missense change has been observed in individual(s) with GM1-gangliosidosis (PMID: 20175788, 35937492). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 555030). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GLB1 function (PMID: 20175788). For these reasons, this variant has been classified as Pathogenic.

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