ClinVar

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 12 of the HNF1A protein (p.Leu12Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of HNF1A-related conditions (PMID: 34789499). ClinVar contains an entry for this variant (Variation ID: 1675062). 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 with a negative predictive value of 80%. This variant disrupts the p.Leu12 amino acid residue in HNF1A. Other variant(s) that disrupt this residue have been observed in individuals with HNF1A-related conditions (PMID: 9287053, 15928245, 31291970), 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.