ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.453del (p.Thr152fs) (rs761863251)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181956 SCV000234259 pathogenic not provided 2018-08-15 criteria provided, single submitter clinical testing The c.453delC pathogenic variant in the KCNH2 gene has been reported in association with LQTS (Swan et al., 1999; Stattin et al., 2012; Park et al., 2013; Christiansen et al., 2014). This variant causes a shift in reading frame starting at codon threonine 152, changing it to a proline, and creating a premature stop codon at position 14 of the new reading frame, denoted p.Thr152ProfsX14. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNH2 gene have been reported in Human Gene Mutation Database in association with LQTS (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.453delC variant has not been observed in large population cohorts (Lek et al., 2016). In summary, c.453delC in the KCNH2 gene is interpreted as a pathogenic variant.
Blueprint Genetics RCV000208221 SCV000263972 pathogenic Long QT syndrome 2 2015-11-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619865 SCV000737442 pathogenic Cardiovascular phenotype 2017-12-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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