ClinVar

Description

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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this variant affects NAGLU protein function (PMID: 16151907). This variant has been observed in individual(s) with mucopolysaccharidosis type IIIB (PMID: 16151907, 30809705). ClinVar contains an entry for this variant (Variation ID: 638092). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces valine with glycine at codon 77 of the NAGLU protein (p.Val77Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine.