Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647833 | SCV000769636 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2022-06-14 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WNK1 protein function. ClinVar contains an entry for this variant (Variation ID: 538505). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. This variant is present in population databases (rs142165599, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 105 of the WNK1 protein (p.Pro105Arg). |
Ambry Genetics | RCV002325290 | SCV002610523 | uncertain significance | Inborn genetic diseases | 2021-02-02 | criteria provided, single submitter | clinical testing | The p.P105R variant (also known as c.314C>G), located in coding exon 1 of the WNK1 gene, results from a C to G substitution at nucleotide position 314. The proline at codon 105 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |