ClinVar Miner

Submissions for variant NM_000219.6(KCNE1):c.227_229delinsTCTA (p.Asp76fs) (rs1555843898)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519587 SCV000617228 uncertain significance not specified 2017-05-31 criteria provided, single submitter clinical testing The c.227_229delACCinsTCTA variant has been reported in one individual referred for LQTS testing, whether thisindividual was referred due to a personal or family history of disease is unknown (Kapplinger et al., 2009). Thisvariant causes a shift in reading frame starting at codon aspartic acid 76, changing it to a valine, and creating apremature stop codon at position 35 of the new reading frame, denoted p.Asp76ValfsX35. This variant is expected toresult in an abnormal, truncated protein product, in which the last 54 amino acids are deleted and replaced by 34different amino acids. Only one other frameshift variant, which is upstream of the c.227_229delACCinsTCTA variant,and a few downstream nonsense variants have been reported in HGMD in association with LQTS (Stenson et al.,2014). The c.227_229delACCinsTCTA variant is also not observed in large population cohorts (Lek et al., 2016;1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, in the absence of functional studies,the consequence of this variant cannot be precisely determined.
GenomeConnect, ClinGen RCV000509561 SCV000607218 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000631568 SCV000752650 uncertain significance Long QT syndrome 2018-10-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KCNE1 gene (p.Asp76Valfs*35). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acids of the KCNE1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of long QT syndrome (Invitae). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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