ClinVar

Description

p.Pro687Leu (CCC>CTC): c.2060 C>T in exon 10 in the GRIN2B gene (NM_000834.3). The P687L variant in the GRIN2B gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P687L 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. The P687L 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 well conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. At least one missense mutation in a nearby residue (R682C) has been reported in association with intellectual disability with behavioral anomalies, supporting the functional importance of this region of the protein. The P687L variant is a good candidate for a disease-causing mutation. However, the possibility it may be a rare benign variant cannot be excluded. The variant is found in GRIN2B panel(s).