Description
The R271Q variant has been reported previously in association with MODY (Tonooka et al., 2002; Bitterman et al., 2016). The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R271Q 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 conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies have shown R271Q results in increased DNA binding ability, reduced transactivation activities, and abnormal cytoplasmic distribution (Balamurugan et al.; 2016). Missense variants in the same residue (R271W/G) and in nearby residues (N266S/K, W267R/S, F268L/S, A269P/D, R272S/H, K273N, A276D/G) have been reported in the Human Gene Mutation Database in association with MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, we consider this variant to be pathogenic.
| # | 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 |
