Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001213328 | SCV001384954 | pathogenic | Long QT syndrome | 2022-08-31 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with Long QT syndrome (PMID: 19862833, 26675252; Invitae). It has also been observed to segregate with disease in related individuals. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 657 of the KCNH2 protein (p.Gly657Cys). ClinVar contains an entry for this variant (Variation ID: 943187). For these reasons, this variant has been classified as Pathogenic. 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: 17823114, 19716085, 26958806; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KCNH2 function (PMID: 18955593). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. |