ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2173_2179dup (p.Gly727fs) (rs1060500603)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464451 SCV000543202 likely pathogenic Early infantile epileptic encephalopathy 2017-01-18 criteria provided, single submitter clinical testing 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. 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. 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. 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.

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