ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.4823C>T (p.Ala1608Val)

gnomAD frequency: 0.00002  dbSNP: rs781667314
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706095 SCV000835127 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2018-06-21 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 valine 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. This variant is present in population databases (rs781667314, ExAC 0.009%). This sequence change replaces alanine with valine at codon 1608 of the WNK1 protein (p.Ala1608Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine.
Fulgent Genetics, Fulgent Genetics RCV000706095 SCV002793415 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2021-10-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004026711 SCV004978883 likely benign Inborn genetic diseases 2023-12-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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