ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.1336G>A (p.Glu446Lys)

dbSNP: rs114625063
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668870 SCV000793543 uncertain significance Mucopolysaccharidosis, MPS-III-B 2017-08-18 criteria provided, single submitter clinical testing
Centogene AG - the Rare Disease Company RCV001250253 SCV001424458 pathogenic Mucopolysaccharidosistype IIIB criteria provided, single submitter clinical testing
Invitae RCV003767969 SCV004571059 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 446 of the NAGLU protein (p.Glu446Lys). This variant is present in population databases (rs114625063, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 33083013). ClinVar contains an entry for this variant (Variation ID: 553423). 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: 14984474, 29979746). For these reasons, this variant has been classified as Pathogenic.

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