ClinVar Miner

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

dbSNP: rs794728438
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181976 SCV000234279 pathogenic not provided 2022-04-18 criteria provided, single submitter clinical testing Identified in a family with LQTS in the published literature (Curran et al., 1995); Not observed in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect as this variant yields a protein unable to form functional potassium channels and results in reduced capacity for potassium transport (Sanguinetti et al., 1996); In-frame deletion of 9 amino acids in a non-repeat region and disrupts the third membrane-spanning domain (S3) of KCNH2, causing loss of normal protein function; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10690299, 8700910, 7889573)
Labcorp Genetics (formerly Invitae), Labcorp RCV003647757 SCV004517273 pathogenic Long QT syndrome 2023-02-28 criteria provided, single submitter clinical testing This variant, c.1498_1524del, results in the deletion of 9 amino acid(s) of the KCNH2 protein (p.Ile500_Phe508del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with long QT syndrome (PMID: 7889573). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 200638). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000015506 SCV000035771 pathogenic Long QT syndrome 2 1995-03-10 no assertion criteria provided literature only

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