ClinVar Miner

Submissions for variant NM_000219.6(KCNE1):c.12dup (p.Asn5Ter) (rs1131691762)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493904 SCV000582777 pathogenic not provided 2015-10-12 criteria provided, single submitter clinical testing The c.12dupT variant in the KCNE1 gene has been observed in an individual referred for LQTS testing and was absent from over 2,600 reference alleles (Kapplinger et al., 2009). This variant causes a shift in reading frame starting at codon Asparagine 5, which creates a premature stop codon at this position of the new reading frame, denoted p.N5X. This pathogenic variant is expected to result in an abnormal, truncated protein product. Other frameshift variants in the KCNE1 gene have been reported in HGMD in association with arrhythmia (Stenson et al., 2014). Furthermore, the c.12dupT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.12dupT in the KCNE1 gene is interpreted as a pathogenic variant.
Invitae RCV000694374 SCV000822817 likely pathogenic Long QT syndrome 2019-02-14 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KCNE1 gene (p.Asn5*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 125 amino acids (97%) of the KCNE1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual undergoing testing for long-QT syndrome (PMID: 19716085). It is also known as 13insT in the literature. At least one missense substitution downstream of this variant (p.Asp76Asn) has been determined to be pathogenic (PMID: 9354802, 24606995, 24400172). This suggests that this region is critical for KCNE1 protein function and that deletion of this region may cause disease. 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.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000493904 SCV001447310 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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