Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000557208 | SCV000649436 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2017-06-08 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on WNK1 function. The available evidence is currently insufficient to determine its role 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a WNK1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with histidine at codon 1516 of the WNK1 protein (p.Pro1516His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. |