Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520263 | SCV000621206 | uncertain significance | not provided | 2017-09-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SPG7 gene. The I743L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I743L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The I743L 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 where amino acids with similar properties to Isoleucine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a different missense substitution at the same position (I743T) in the SPG7 gene has been reported previously along with a second variant in multiple individuals with ataxia, upper motor neuron syndrome, and progressive external ophthalmoplegia (Brugman et al., 2008; van Gassen et al., 2012; Pfeffer et al., 2014; Pfeffer et al., 2015, Yang et al., 2016). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |