Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051709 | SCV001215877 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 158 of the WNK1 protein (p.Ser158Thr). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 848039). 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 with a negative predictive value of 95%. 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. |
| Illumina Laboratory Services, |
RCV001113717 | SCV001271508 | uncertain significance | Pseudohypoaldosteronism type 2C | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Ambry Genetics | RCV002339260 | SCV002638337 | uncertain significance | Inborn genetic diseases | 2021-09-08 | criteria provided, single submitter | clinical testing | The p.S158T variant (also known as c.473G>C), located in coding exon 1 of the WNK1 gene, results from a G to C substitution at nucleotide position 473. The serine at codon 158 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine 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. |