ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.1968_1969delinsTT (p.Gly657Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001213328 SCV001384954 likely pathogenic Long QT syndrome 2019-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 657 of the KCNH2 protein (p.Gly657Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals affected with long QT syndrome (PMID: 26675252, 19862833). This variant has been reported to affect KCNH2 protein function (PMID: 18955593). This variant disrupts the p.Gly657 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19716085, 26958806, 17823114, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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