ClinVar

Description

Experimental studies have shown that this missense change affects AGA function (PMID: 27876883). For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AGA protein function. ClinVar contains an entry for this variant (Variation ID: 557564). This missense change has been observed in individual(s) with aspartylglucosaminuria (PMID: 27876883, 30564628). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs771563230, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 122 of the AGA protein (p.Thr122Lys).