Submissions for variant NM_000263.4(NAGLU):c.1973A>G (p.Tyr658Cys) (rs1230894568)

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Total submissions: 1

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000693826	SCV000822245	pathogenic	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V	2019-11-26	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine with cysteine at codon 658 of the NAGLU protein (p.Tyr658Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Sanfilippo syndrome in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 572445). 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.Tyr658 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been observed in individuals with NAGLU-related conditions (PMID: 11286389), which suggests that this may be a clinically significant amino acid residue. For these reasons, this allele has been classified as Pathogenic.

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