Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244579 | SCV001417808 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-10-28 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 969273). Disruption of this splice site has been observed in individual(s) with epileptic encephalopathy (PMID: 25951140). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the KCNQ2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KCNQ2 are known to be pathogenic (PMID: 14534157, 23692823, 27779742). For these reasons, this variant has been classified as Pathogenic. |