ClinVar Miner

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 2020-10-18 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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