Description
The R655H variant in the STRA6 gene has been reported previously in the compound heterozygous state, opposite of a second STRA6 missense variant, in an individual with PDAC syndrome, characterized by bilateral colobomatous microphthalmia, patent ductus arteriosus, broad, bushy eyebrows, broad nasal bridge, retrognathia, large ears with otherwise normal development (Segel et al., 2009). The R655H 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 R655H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A different, but same codon variant (R655C) has been reported in the Human Gene Mutation Database in association with an STRA6-related disorder (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret the R655H variant as a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
| # | 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 |
