ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1704_1708dup (p.Pro570fs) (rs794728449)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181987 SCV000234290 likely pathogenic not provided 2017-08-17 criteria provided, single submitter clinical testing Although the c.2724_2728dupGGGGC likely pathogenic variant in the KCNH2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Proline 910, changing it to an Arginine, and creating a premature stop codon at position 66 of the new reading frame, denoted p.Pro910ArgfsX66. This 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 HGMD in association with LQTS (Stenson et al., 2014). The c.2724_2728dupGGGGC variant was not observed in approximately 2,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. In summary, c.2724_2728dupGGGGC in the KCNH2 gene is expected to be pathogenic.
Invitae RCV000631709 SCV000752796 pathogenic Long QT syndrome 2017-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro910Argfs*66) 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 not been reported in the literature in individuals with KCNH2-related disease. ClinVar contains an entry for this variant (Variation ID: 200660). 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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