Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000518859 | SCV000619628 | uncertain significance | not provided | 2017-08-02 | criteria provided, single submitter | clinical testing | The c.1076T>G variant in the GLI3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1076T>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice models predict that c.1076T>G may create a cryptic splice acceptor site in exon 8, however the natural splice acceptor site is unaffected. In the absence of RNA/functional studies, the actual effect of the c.1076T>G change in this individual is unknown. If c.1076T>G does not alter splicing, it will result in the M359R missense change. The M359R 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 where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret c.1076T>G as a variant of uncertain significance. |