ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1096C>T (p.Arg366Ter) (rs794728364)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181779 SCV000234082 pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing The R366X pathogenic variant in the KCNH2 gene has been reported previously in association with LQTS (Larsen et al., 2001; Tester D et al., 2005; Zhang X et al., 2008; Christiansen et al., 2014). The patient reported by Zhang et al. (2008) also presented with bradycardia, torsades de pointes, syncope, and first degree AV block. Additionally, another report identified R366X in one individual with LQTS and a personal history of seizures (Johnson J et al., 2009). R366X, located in the N-terminal region of the protein, is predicted to cause loss of normal protein function either due to a prematurely truncated protein or absent protein product due to nonsense mediated mRNA decay. Other nonsense variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the R366X 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, R366X in the KCNH2 gene is interpreted as a pathogenic variant.

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