ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.3899C>T (p.Ser1300Phe)

gnomAD frequency: 0.00003  dbSNP: rs143361850
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000281301 SCV000381966 benign Pseudohypoaldosteronism type 2C 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001240672 SCV001413640 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1552 of the WNK1 protein (p.Ser1552Phe). This variant is present in population databases (rs143361850, gnomAD 0.009%). 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: 310825). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt WNK1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002338889 SCV002636825 uncertain significance Inborn genetic diseases 2022-01-31 criteria provided, single submitter clinical testing The p.S1552F variant (also known as c.4655C>T), located in coding exon 19 of the WNK1 gene, results from a C to T substitution at nucleotide position 4655. The serine at codon 1552 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001240672 SCV005631693 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C 2024-04-10 criteria provided, single submitter clinical testing

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