ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2007C>G (p.Tyr669Ter) (rs1057520558)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000423718 SCV000516037 pathogenic not provided 2015-03-31 criteria provided, single submitter clinical testing The Y1009X variant in the KCNH2 gene has not been reported as a pathogenic variant or as a benign polymorphism to our knowledge. Y1009X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson P et al., 2014). The Y1009X variant was not observed in approximately 6100 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, Y1009X in the KCNH2 gene is interpreted as a pathogenic variant.
Invitae RCV000804954 SCV000944894 pathogenic Long QT syndrome 2018-08-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1009*) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage 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: 379293). 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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