CPT® Code 81320

Molecular genetic testing is a critical procedure used to identify specific mutations within the PLCG2 (phospholipase C gamma 2) gene, particularly those common variants associated with chronic lymphocytic leukemia (CLL). The PLCG2 gene is situated on the long (q) arm of chromosome 16 at position 23.3 (16q23.3) and encodes a transmembrane signaling enzyme that plays a vital role in cellular communication. This enzyme utilizes calcium to facilitate the conversion of inositol trisphosphate (IP3) and diacylglycerol (DAG), which are essential for transporting growth factor and immune system receptors across cell membranes. The specific mutations identified through this testing include R665W, S707F, and L845F, all of which are single amino acid substitution mutations that lead to a gain of function in the enzyme's activity. The R665W mutation, occurring on exon 19 of the SH domain, replaces arginine with tryptophan. The S707F mutation, found on exon 20 of the SH domain, substitutes serine with phenylalanine. Lastly, the L845F mutation, located on exon 24 of the PH domain, involves the substitution of leucine with phenylalanine. These mutations are significant as they are linked to resistance against commonly prescribed CLL treatments such as ibrutinib and acalabrutinib. The testing for these variants may be conducted prior to the initiation of treatment and/or during the course of treatment to inform therapeutic decisions. The CPT® Code 81320 specifically reports the analysis of the PLCG2 gene to identify these common functional variants by comparing gene segments to ascertain similarities or differences and to elucidate relationships among them.