ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1513dup (p.Arg505fs) (rs397508105)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459335 SCV000543307 likely pathogenic Long QT syndrome 2017-03-15 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 16 of the KCNQ1 mRNA (c.1894dupA), causing a frameshift at codon 632. This creates a premature translational stop signal in the last exon of the KCNQ1 mRNA (p.Arg632Lysfs*20). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acids of the KCNQ1 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNQ1-related disease. A different truncation in KCNQ1 nearly identical to this variant (c.1893delC, p.Arg632Glnfs*20) has been determined to be pathogenic (PMID: 10024302, 10973849, 19825999, 23098067, 23631430, 25187895). This suggests that deletion of this region of the KCNQ1 protein is causative of disease. In summary, this variant is a novel insertion that is similar to a previously described pathogenic insertion. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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