Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001944595 | SCV002132726 | uncertain significance | Long QT syndrome | 2021-10-03 | 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.Asp774 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been observed in individuals with KCNH2-related conditions (PMID: 5417810, 22429796), 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with clinical features of long QT syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with valine at codon 774 of the KCNH2 protein (p.Asp774Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. |