Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001202682 | SCV001373805 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2022-01-28 | criteria provided, single submitter | clinical testing | 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: 934320). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. This variant is present in population databases (rs780699781, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 63 of the WNK1 protein (p.Lys63Gln). 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. |
| ARUP Laboratories, |
RCV001812245 | SCV001473386 | uncertain significance | not provided | 2019-09-16 | criteria provided, single submitter | clinical testing | The WNK1 c.187A>C; p.Lys63Gln variant (rs780699781), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on only four chromosomes (4/273990 alleles) in the Genome Aggregation Database. The lysine at codon 63 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Lys63Gln variant is uncertain at this time. |
| Ambry Genetics | RCV002411737 | SCV002721142 | uncertain significance | Inborn genetic diseases | 2022-09-30 | criteria provided, single submitter | clinical testing | The p.K63Q variant (also known as c.187A>C), located in coding exon 1 of the WNK1 gene, results from an A to C substitution at nucleotide position 187. The lysine at codon 63 is replaced by glutamine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all available 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. |
| Fulgent Genetics, |
RCV001202682 | SCV002787157 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2022-04-10 | criteria provided, single submitter | clinical testing |