ClinVar

Description

p.Thr684Ala (ACA>GCA): c.2050 A>G in exon 11 of the GRIN2A gene (NM_000833.3). The T684A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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 T684A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position in the predicted extracellular loop between the second and third transmembrane domains of the GRIN2A protein, and other missense mutations in this region of the protein have been reported in association with GRIN2A-related disorders, supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).