Description
The G231R variant was identified previously in a female with seizures and intellectual and developmental disabilities; however, no additional information was provided to unequivocally demonstrate that it is pathogenic and parental studies were not performed (Sundaram et al., 2014). 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 G231R 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 occurs at a position that is conserved in mammals, and missense variants in a nearby residue (P225R, P225T) have been reported in RettBASE and the Human Gene Mutation Database in association with Rett syndrome (MECP2 Variation Database; Stenson et al., 2014). However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
