ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.4474G>A (p.Val1492Ile)

gnomAD frequency: 0.00004  dbSNP: rs774954731
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546794 SCV000649435 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2021-03-28 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with WNK1-related disease. ClinVar contains an entry for this variant (Variation ID: 471189). This variant is present in population databases (rs774954731, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 1492 of the WNK1 protein (p.Val1492Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine.
Ambry Genetics RCV002341407 SCV002645339 uncertain significance Inborn genetic diseases 2022-01-11 criteria provided, single submitter clinical testing The p.V1744I variant (also known as c.5230G>A), located in coding exon 19 of the WNK1 gene, results from a G to A substitution at nucleotide position 5230. The valine at codon 1744 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well 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.

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