ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.685G>T (p.Glu229Ter) (rs730880116)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412861 SCV000490548 pathogenic not provided 2016-09-09 criteria provided, single submitter clinical testing The E229X pathogenic variant in the KCNH2 gene has been previously reported in multiple individuals in association with LQTS (Tester et al., 2005; Tester et al., 2006; Berge et al., 2008; Goldenberg et al., 2011). This variant was also observed in one affected individual from a family referred for LQTS genetic testing at GeneDx, and was found to segregate with a prolonged QT interval in a second family member. E229X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Furthermore, multiple other nonsense variants in the KCNH2 gene have been reported in the Human Gene Mutation Database in association with LQTS (Stenson et al., 2014). Finally, while data from control individuals was not sufficient to assess whether E229X may be a common benign variant in the general population, Tester et al. (2005) previously reported E229X to be absent from over 1,400 reference alleles.In summary, E229X in the KCNH2 gene is interpreted as a pathogenic variant.
Invitae RCV000545572 SCV000627495 pathogenic Long QT syndrome 2017-09-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu229*) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in multiple individuals referred for long QT syndrome testing (PMID: 15840476, 16818214, 18752142, 19716085). ClinVar contains an entry for this variant (Variation ID: 180379). Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 19862833). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000157258 SCV000206988 pathogenic Long QT syndrome 2 2014-10-07 no assertion criteria provided clinical testing

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