Submissions for variant NM_000263.4(NAGLU):c.2020C>T (p.Arg674Cys) (rs763299645)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668435	SCV000793035	likely pathogenic	Mucopolysaccharidosis, MPS-III-B	2017-07-27	criteria provided, single submitter	clinical testing
Invitae	RCV001248721	SCV001422227	pathogenic	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V	2019-11-05	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 674 of the NAGLU protein (p.Arg674Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs763299645, ExAC 0.007%). This variant has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 9443875, 10094189). 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: 553061). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg674 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8650226, 9443875, 9950362, 20852935). 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.

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