Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520134 | SCV000621758 | uncertain significance | not provided | 2017-10-25 | criteria provided, single submitter | clinical testing | The c.1930 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1930 G>A variant is not observed in large population cohorts (Lek et al., 2016). Multiple in-silico splice prediction models predict that c.1930 G>A destroys the natural splice donor site and may lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.1930 G>A on splicing in this individual is unknown. If c.1930 G>A does not alter splicing, it will result in the D644N missense change. The D644N substitution occurs at a position where amino acids with similar properties to Asparagine are tolerated across species. However, this variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (V640G, M646V/I) have been reported in the Human Gene Mutation Database in association with myotonia congenita (Stenson et al., 2014), supporting the functional importance of this region of the protein. |