ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2087del (p.Gly696fs) (rs794728469)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182064 SCV000234367 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing The c.3107delG variant in the KCNH2 gene has been reported in one individual with a suspected diagnosis of LQTS (Lieve et al., 2013). This variant causes a shift in reading frame starting at codon Glycine 1036, changing it to an Alanine, and creating a premature stop codon at position 21 of the new reading frame, denoted p.Gly1036AlafsX21. 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.3107delG variant was not observed in approximately 5,600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project (read depth: 4.0).In summary, c.3107delG in the KCNH2 gene is expected to be pathogenic, as loss of function variants in this gene are strongly associated with this phenotype
Invitae RCV000469782 SCV000543463 pathogenic Long QT syndrome 2017-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly1036Alafs*21) 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 been reported in individuals affected with or with suspicion of long QT syndrome or sudden arrhythmic death syndrome (PMID: 28449774, 23631430). 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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