ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.545C>A (p.Ser182Ter) (rs1057517742)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413351 SCV000490547 pathogenic not provided 2017-01-05 criteria provided, single submitter clinical testing The S182X pathogenic variant, located in the N-terminus of the KCNH2 gene, has been previously reported in association with Long QT syndrome and was absent in 1,488 alleles from healthy control individuals of four different ethnic backgrounds (Tester D et al., 2005). S182X is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, other nonsense variants in the KCNH2 gene have been reported in association with LQTS, further supporting the functional importance of this region of the protein (Stenson P et al., 2014). In summary, S182X in the KCNH2 gene is interpreted as a pathogenic variant.
Invitae RCV000686182 SCV000813686 pathogenic Long QT syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser182*) 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 an individual referred for long QT syndrome genetic testing (PMID: 15840476). ClinVar contains an entry for this variant (Variation ID: 372376). 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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