ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1880dup (p.Pro628fs) (rs786204101)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168023 SCV000218675 pathogenic Long QT syndrome 2014-10-11 criteria provided, single submitter clinical testing This sequence change duplicates a C nucleotide in exon 12 of the KCNH2 mRNA (c.2900dupC), causing a frameshift at codon 968. This creates a premature translational stop signal (p.Pro968Alafs*151) and is expected to result in an absent or truncated protein product. This sequence change has been reported in one individual affected with long QT syndrome (PMID: 18752142) and is not present in population databases. Truncating sequence changes in KCNH2 are known to be pathogenic (PMID: 10973849, 17576861). In summary, this is a truncating sequence change which is not reported in population databases, and has been observed in in one individual affected with long QT. For these reasons, this sequence change has been classified as Pathogenic
GeneDx RCV000182001 SCV000234304 pathogenic not provided 2016-01-18 criteria provided, single submitter clinical testing The c.2900dupC pathogenic variant in the KCNH2 gene has been reported previously in association with LQTS (Berge et al., 2008; Seethala et al., 2015). The c.2900dupC varaint causes a shift in reading frame starting at codon Proline 968, changing it to an Alanine, and creating a premature stop codon at position 151 of the new reading frame, denoted p.Pro968AlafsX151. This pathogenic variant is expected to result in an abnormal protein product. Other frameshift variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.2900dupC variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project (average read depth 9.0).

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