ClinVar

Description

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 366 of the GALNT3 protein (p.Leu366Arg). This variant is present in population databases (rs780440401, gnomAD 0.02%). This missense change has been observed in individual(s) with tumoral calcinosis (PMID: 19830424). 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. 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 GALNT3 protein function with a positive predictive value of 80%. 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.