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 GALT 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. This variant disrupts the p.His186 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22944367, 20547145, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in individual(s) with clinical features of GALT-related conditions (PMID: 17486650). ClinVar contains an entry for this variant (Variation ID: 439749). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with asparagine at codon 186 of the GALT protein (p.His186Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine.