ClinVar Miner

Submissions for variant NM_000219.6(KCNE1):c.1A>T (p.Met1Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001376771 SCV001573935 likely pathogenic Long QT syndrome 2020-08-23 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the KCNE1 mRNA. The next in-frame methionine is located at codon 27. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNE1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the initiator methionine in KCNE1. If translation initiates from the next in-frame methionine, the KCNE1 protein would no longer include the region containing the p.Thr7 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with KCNE1-related conditions (PMID: 9354783), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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