ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.765G>C (p.Gln255His)

dbSNP: rs1553610553
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670551 SCV000795414 likely pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-11-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767987 SCV004604050 likely pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 255 of the GLB1 protein (p.Gln255His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GM1 gangliosidosis (PMID: 16617000, 19472408, 25600812). ClinVar contains an entry for this variant (Variation ID: 554850). 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: 19472408). 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.

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