Description
A variant that is likely pathogenic has been identified in the STXBP1 gene. The G236D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G236D variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G236D 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (I232N, R235G/Q) have been either observed at GeneDx or reported in association with STXBP1-related disorders (Stenson et al., 2014). However, this substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. Therefore, this variant is likely pathogenic; however, the possibility that it is benign 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 |
