Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756938 | SCV000884929 | uncertain significance | not provided | 2018-02-22 | criteria provided, single submitter | clinical testing | The WNK1 c.130G>A; p.Ala44Thr variant (rs764240024), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.0008% (identified on 2 out of 236,264 chromosomes). The alanine at position 44 is weakly conserved, considering 18 species, and computational analyses of the effects of the p.Ala44Thr variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ala44Thr variant cannot be determined with certainty. |
| Invitae | RCV001855884 | SCV002262498 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2023-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 44 of the WNK1 protein (p.Ala44Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WNK1 protein function. ClinVar contains an entry for this variant (Variation ID: 618496). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. |
| Fulgent Genetics, |
RCV001855884 | SCV002775666 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C | 2021-09-10 | criteria provided, single submitter | clinical testing |