Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485443 | SCV000572004 | likely pathogenic | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | The G294R pathogenic variant in the FBP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The G294R 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 G294R 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 across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Two different missense variants affecting the same residue (G294E, G294V) have been reported in the Human Gene Mutation Database in association with fructose-1,6-bisphosphatase deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret G294R as a likely pathogenic variant |