ClinVar

Description

This variant disrupts the p.Cys265 amino acid residue in NPHS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17290294, 19443487). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. 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 NPHS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1339085). This variant has not been reported in the literature in individuals affected with NPHS1-related conditions. This variant is present in population databases (rs748287435, gnomAD 0.02%). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 265 of the NPHS1 protein (p.Cys265Ser).