Submissions for variant NM_018979.4(WNK1):c.3991C>A (p.Pro1331Thr)

dbSNP: rs200513331

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000707100	SCV000836181	uncertain significance	Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C	2023-06-27	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. 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: 582910). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. This variant is present in population databases (rs200513331, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1583 of the WNK1 protein (p.Pro1583Thr).
Mayo Clinic Laboratories, Mayo Clinic	RCV001700295	SCV004226276	uncertain significance	not provided	2023-06-02	criteria provided, single submitter	clinical testing	BP4
Clinical Genetics, Academic Medical Center	RCV001700295	SCV001925780	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700295	SCV001970153	uncertain significance	not provided		no assertion criteria provided	clinical testing