ClinVar

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 161 of the HNF1A protein (p.Ala161Thr). This variant is present in population databases (rs201095611, gnomAD 0.02%). This missense change has been observed in individuals with HNF1A-related conditions (PMID: 9754819, 21224407, 23517481, 23869231, 32041611). ClinVar contains an entry for this variant (Variation ID: 972757). 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 not expected to disrupt HNF1A protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on HNF1A function (PMID: 32910913). This variant disrupts the p.Ala161 amino acid residue in HNF1A. Other variant(s) that disrupt this residue have been observed in individuals with HNF1A-related conditions (PMID: 23517481), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.