ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.418G>A (p.Ala140Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803066 SCV000942924 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Pseudohypoaldosteronism type 2C 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 140 of the WNK1 protein (p.Ala140Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with WNK1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The threonine 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. 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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