ClinVar

Description

The P197L variant has been reported as a disease-causing variant in a study examining the cost-effectiveness of genetic testing in inherited heart disease (Sabater-Molina et al., 2013). Clinical information was not provided. The P197L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P197L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. The P197 residue is located in the S3 transmembrane helix. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (F193L, A194P, R195W, I198V, S199A, D202H) have been reported in the Human Gene Mutation Database in association with LQTS (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, additional evidence is needed to determine whether this variant is pathogenic or benign.