ClinVar Miner

Submissions for variant NM_213655.5(WNK1):c.2605C>A (p.Leu869Ile)

gnomAD frequency: 0.00011  dbSNP: rs377073379
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000237034 SCV000293149 uncertain significance not provided 2015-09-22 criteria provided, single submitter clinical testing The L869I variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The L869I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001052902 SCV001217137 likely benign Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-01-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV001334035 SCV001526770 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A 2018-11-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV000237034 SCV001714998 uncertain significance not provided 2020-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002429149 SCV002740693 uncertain significance Inborn genetic diseases 2022-04-06 criteria provided, single submitter clinical testing The p.L869I variant (also known as c.2605C>A), located in coding exon 10 of the WNK1 gene, results from a C to A substitution at nucleotide position 2605. The leucine at codon 869 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in 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.

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