ClinVar Miner

Submissions for variant NM_000238.3(KCNH2):c.1498_1524del27 (p.Ile500_Phe508del) (rs794728438)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181976 SCV000234279 pathogenic not provided 2019-01-15 criteria provided, single submitter clinical testing The c.1498_1524del27 pathogenic variant in the KCNH2 gene has been previously reported to segregate with disease in a family with LQTS (Curran et al., 1995). Additionally, this variant has not been observed in large population cohorts (Lek et al., 2016), indicating it is not a common benign variant. The c.1498_1524del27 variant results in the in-frame deletion of nine amino acids, and disrupts the third membrane-spanning domain (S3) of KCNH2, causing loss of normal protein function. Sanguinetti et al. (1996) performed functional studies which demonstrated the c.1498_1524del27 variant yields a protein unable to form functional potassium channels and results in reduced capacity for potassium transport. Furthermore, other in-frame deletions/duplications in the KCNH2 gene have been reported in the Human Gene Mutation Database in association with LQTS (Stenson et al., 2014).
OMIM RCV000015506 SCV000035771 pathogenic Long QT syndrome 2 1995-03-10 no assertion criteria provided literature only

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