ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.1001G>A (p.Arg334Gln)

gnomAD frequency: 0.00003  dbSNP: rs281864970
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001852647 SCV002245601 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 334 of the GNPTAB protein (p.Arg334Gln). This variant is present in population databases (rs281864970, gnomAD 0.003%). This missense change has been observed in individuals with mucolipidosis (PMID: 19617216, 32651481). ClinVar contains an entry for this variant (Variation ID: 39018). 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 GNPTAB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GNPTAB function (PMID: 25505245). This variant disrupts the p.Arg334 amino acid residue in GNPTAB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19197337, 25505245; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000032283 SCV000055926 not provided Pseudo-Hurler polydystrophy no assertion provided literature only

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