ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.187A>C (p.Lys63Gln)

gnomAD frequency: 0.00004  dbSNP: rs780699781
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001202682 SCV001373805 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2022-01-28 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 63 of the WNK1 protein (p.Lys63Gln). This variant is present in population databases (rs780699781, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 934320). 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. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812245 SCV001473386 uncertain significance not provided 2019-09-16 criteria provided, single submitter clinical testing The WNK1 c.187A>C; p.Lys63Gln variant (rs780699781), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on only four chromosomes (4/273990 alleles) in the Genome Aggregation Database. The lysine at codon 63 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Lys63Gln variant is uncertain at this time.
Ambry Genetics RCV002411737 SCV002721142 uncertain significance Inborn genetic diseases 2022-09-30 criteria provided, single submitter clinical testing The p.K63Q variant (also known as c.187A>C), located in coding exon 1 of the WNK1 gene, results from an A to C substitution at nucleotide position 187. The lysine at codon 63 is replaced by glutamine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all 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.
Fulgent Genetics, Fulgent Genetics RCV001202682 SCV002787157 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-05-09 criteria provided, single submitter clinical testing

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