Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187933 | SCV000241535 | pathogenic | not provided | 2013-11-12 | criteria provided, single submitter | clinical testing | The Glu749Stop nonsense mutation in the KCNQ2 gene is predicted to cause loss of normal protein function through protein truncation, as the last 124 amino acids of the protein are lost. Although this mutation has not been reported previously to our knowledge, its presence is consistent with a diagnosis of a KCNQ2-related disorder. The variant is found in EPILEPSY panel(s). |
Invitae | RCV000636309 | SCV000757748 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu749*) in the KCNQ2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the KCNQ2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with in a cohort of individuals tested for epilepsy and/or neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 205931). This variant disrupts a region of the KCNQ2 protein in which other variant(s) (p.Cys774Leufs*91) have been determined to be pathogenic (PMID: 23692823). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |