ClinVar

Description

This missense change has been observed in individuals with nonsyndromic enlarged vestibular aqueduct (PMID: 17718863, 23918157, 25372295). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 532 of the SLC26A4 protein (p.Ser532Ile). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 370114). 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 SLC26A4 protein function. This variant disrupts the p.Ser532 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17718863, 23918157, 25372295). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.