ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.841C>T (p.His281Tyr) (rs745386663)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413217 SCV000490540 pathogenic not provided 2016-11-02 criteria provided, single submitter clinical testing The H281Y variant in the GLB1 gene has previously been reported in association with both GM1-gangliosidosis and Morquio B disease (Paschke et al., 2001; Gucev et al., 2008; Ong et al., 2012; Coutinho et al., 2012). Individuals homozygous for H281Y have been reported to have infantile onset GM1-gangliosidosis (Ong et al., 2012; Coutinho et al., 2012). The H281Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore we interpret H281Y to be a pathogenic variant.
Invitae RCV000805468 SCV000945425 pathogenic Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2020-09-01 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 281 of the GLB1 protein (p.His281Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs745386663, ExAC 0.006%). This variant has been observed in individual(s) with GLB1-related conditions (PMID: 11511921, 15714521, 18546276, 21497194, 21214877). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372371). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV000662341 SCV000784706 not provided Mucopolysaccharidosis, MPS-IV-B no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Counsyl RCV000662341 SCV000791787 likely pathogenic Mucopolysaccharidosis, MPS-IV-B 2017-05-23 no assertion criteria provided clinical testing

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