ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1255C>T (p.Arg419Trp)

gnomAD frequency: 0.00001  dbSNP: rs747709527
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001250224 SCV001424429 pathogenic GM1 gangliosidosis criteria provided, single submitter clinical testing
Invitae RCV001349145 SCV001543473 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2023-11-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 419 of the GLB1 protein (p.Arg419Trp). This variant is present in population databases (rs747709527, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of GM1 gangliosidosis and/or GLB1-related conditions (PMID: 31761138, 33083013). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1399C>T p.(Arg467Trp). ClinVar contains an entry for this variant (Variation ID: 973576). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003238855 SCV003936697 likely pathogenic not provided 2022-12-29 criteria provided, single submitter clinical testing 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: 31761138, 33083013)

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