ClinVar

Description

This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2783 of the FBN1 protein (p.Ala2783Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Marfan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 1518035). 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 FBN1 protein function with a positive predictive value of 95%. This variant disrupts the p.Ala2783 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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.