ClinVar

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 50 of the TTR protein (p.Val50Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of familial transthyretin amyloidosis (PMID: 1520326, 19922332, 27212199). This variant is also known as p.Val30Leu. ClinVar contains an entry for this variant (Variation ID: 2138144). 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 TTR protein function with a positive predictive value of 95%. This variant disrupts the p.Val50 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22620962, 23833285, 24555660). 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.