Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000803013 | SCV000942866 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2024-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2551 of the WNK1 protein (p.Leu2551Val). This variant is present in population databases (rs143616411, gnomAD 0.008%). 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: 648308). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Ambry Genetics | RCV002388494 | SCV002674156 | uncertain significance | Inborn genetic diseases | 2022-08-08 | criteria provided, single submitter | clinical testing | The p.L2551V variant (also known as c.7651C>G), located in coding exon 28 of the WNK1 gene, results from a C to G substitution at nucleotide position 7651. The leucine at codon 2551 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in 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. |
| Gene |
RCV004723209 | SCV005332643 | uncertain significance | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |