ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.235G>A (p.Gly79Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003069089 SCV003466011 likely pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V 2024-04-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 79 of the NAGLU protein (p.Gly79Ser). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NAGLU-related conditions. ClinVar contains an entry for this variant (Variation ID: 2154072). 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 NAGLU protein function with a positive predictive value of 95%. This variant disrupts the p.Gly79 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9950362, 21712855, 33747789). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Ambry Genetics RCV004071763 SCV004960808 uncertain significance Inborn genetic diseases 2021-02-09 criteria provided, single submitter clinical testing The c.235G>A (p.G79S) alteration is located in exon 1 (coding exon 1) of the NAGLU gene. This alteration results from a G to A substitution at nucleotide position 235, causing the glycine (G) at amino acid position 79 to be replaced by a serine (S). The p.G79S alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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