Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001224330 | SCV001396520 | uncertain significance | Long QT syndrome | 2020-02-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with KCNH2-related conditions. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glycine with aspartic acid at codon 236 of the KCNH2 protein (p.Gly236Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |