Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000464451 | SCV000543202 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2017-01-12 | criteria provided, single submitter | clinical testing | In summary, this is a novel frameshift variant that occurs upstream of a previously described pathogenic frameshift variant. This evidence indicates that the variant is also pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. A different frameshift downstream of this variant (p.Cys744Leufs*91) has been determined to be pathogenic (PMID: 23692823). This suggests that disruption of this region of the KCNQ2 protein is causative of disease. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNQ2-related disease. This sequence change inserts 7 nucleotides in exon 17 of the KCNQ2 mRNA (c.2173_2179dupCGCCAGG), causing a frameshift at codon 727. This creates a premature translational stop signal in the last exon of the KCNQ2 mRNA (p.Gly727Alafs*140). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 145 amino acids of the KCNQ2 protein. |