ClinVar

Description

A variant of uncertain significance has been identified in the LAMP2 gene. The E334Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The E334Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In addition, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014). Furthermore, although this variant was previously identified in one other unrelated individual referred for cardiomyopathy genetic testing at GeneDx, family studies were not performed to discern whether this variant co-segregates with disease.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.