Description
The P82R variant has been reported previously in combination with the M252T variant in individuals withCOACH syndrome and Joubert syndrome related disorder (JSRD) without clinically apparent liver disease(Doherty et al., 2010). It was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations. The P82R variant is a non-conservative amino acid substitution, which is likely to impactsecondary protein structure as these residues differ in polarity, charge, size and/or other properties. Thissubstitution occurs at a position that is conserved across species. Additionally, a different missense variant atthe same residue (P82S) and in a nearby residue (N90K) have been reported in association with TMEM67-related disorders, supporting the functional importance of this region of the protein (Doherty et al., 2010;Iannicelli et al., 2010). We interpret P82R as a pathogenic 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 |
