Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520011 | SCV000620968 | likely pathogenic | not provided | 2017-09-19 | criteria provided, single submitter | clinical testing | The M578T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M578T variant is not observed in large population cohorts (Lek et al., 2016). This 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, and different missense variants at the same position (M578I/V) have been reported in individuals with KCNQ2-related disorders, including as a de novo variant in an individual with neonatal epilepsy (Numis et al., 2014; Grinton et al., 2015). Additionally, missense variants in nearby residues (R581G/Q) have been reported in the Human Gene Mutation Database in association with KCNQ2-related disorders (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function. |