ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1701del (p.Trp568fs) (rs794728440)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181978 SCV000234281 likely pathogenic not provided 2017-01-11 criteria provided, single submitter clinical testing The c.1701delC variant in the KCNH2 gene has been previously reported in association with LQTS (Napolitano C et al., 2005). The c.1701delC variant in the KCNH2 gene causes a shift in reading frame at codon Tryptophan 568, changing it to a Glycine, and creates a premature Stop codon at position 26 of the new reading frame. This variant is expected to result in an abnormal, truncated protein or in absence of protein from this allele due to mRNA decay. In addition, c.1701delC 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. Other frameshift variants in the KCNH2 gene have been reported in association with LQTS. In summary, c.1701delC in the KCNH2 gene is interpreted as a disease-causing variant.
Invitae RCV000631682 SCV000752765 pathogenic Long QT syndrome 2017-08-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp568Glyfs*26) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with long QT syndrome (PMID: 16414944). ClinVar contains an entry for this variant (Variation ID: 200642). Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 19862833). For these reasons, this variant has been classified as Pathogenic.

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