ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.5731G>A (p.Gly1911Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002356230 SCV002654788 uncertain significance Inborn genetic diseases 2022-06-11 criteria provided, single submitter clinical testing The p.G2163S variant (also known as c.6487G>A), located in coding exon 24 of the WNK1 gene, results from a G to A substitution at nucleotide position 6487. The glycine at codon 2163 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, serine 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.
Revvity Omics, Revvity RCV003491096 SCV004237548 uncertain significance not provided 2023-06-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005215847 SCV005852106 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2163 of the WNK1 protein (p.Gly2163Ser). This variant is present in population databases (rs766411372, gnomAD 0.002%). 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: 1753793). 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.

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