ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.1364A>G (p.Tyr455Cys)

dbSNP: rs375103824
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078454 SCV000110310 uncertain significance not provided 2018-05-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001854380 SCV002186033 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V 2024-07-20 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 455 of the NAGLU protein (p.Tyr455Cys). This variant is present in population databases (rs375103824, gnomAD 0.01%). This missense change has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 9443875). ClinVar contains an entry for this variant (Variation ID: 92691). 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%. Experimental studies have shown that this missense change affects NAGLU function (PMID: 29979746). For these reasons, this variant has been classified as Pathogenic.

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