ClinVar

Description

The I46V variant has not been published as pathogenic or been reported as a benign variant to our knowledge. The I46V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. However, the I46V variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although not in any known functional domain, missense variants in nearby residues (S43N, R44S, A45S, A45T, V48M) have been reported in the Human Gene Mutation Database in association with amyloidosis (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign