ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2245G>T (p.Glu749Ter)

dbSNP: rs796052658
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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.

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