Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001236435 | SCV001409158 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2019-09-17 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 has not been reported in the literature in individuals with PCDH19-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with proline at codon 523 of the PCDH19 protein (p.His523Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. |