Total submissions: 1
| 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. |