ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 139 of the HTRA1 protein (p.Ser139Ala). This variant is present in population databases (rs530087850, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (PMID: 25929831). ClinVar contains an entry for this variant (Variation ID: 447571). 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 not expected to disrupt HTRA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.