ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 350 of the NPHS1 protein (p.Ser350Pro). This variant is present in population databases (rs386833863, gnomAD 0.003%). This missense change has been observed in individuals with congenital nephrotic syndrome (PMID: 9915943, 20172850, 20507940, 27594755). ClinVar contains an entry for this variant (Variation ID: 56419). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NPHS1 protein function. Experimental studies have shown that this missense change affects NPHS1 function (PMID: 11726550, 15213260). This variant disrupts the p.Ser350 amino acid residue in NPHS1. Other variant(s) that disrupt this residue have been observed in individuals with NPHS1-related conditions (PMID: 27325253), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.