Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002021198 | SCV002298710 | uncertain significance | Long QT syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg744 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been observed in individuals with KCNH2-related conditions (PMID: 22314138, 26746457), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1515578). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is present in population databases (rs189014161, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 744 of the KCNH2 protein (p.Arg744Gly). |