ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 206 of the TPP1 protein (p.Arg206Cys). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg206 amino acid residue in TPP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12698559; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects TPP1 function (PMID: 20340139). 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 TPP1 protein function. ClinVar contains an entry for this variant (Variation ID: 2646). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 22832778, 30541466). This variant is present in population databases (rs28940573, gnomAD 0.003%).