ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.2468A>G (p.His823Arg) (rs56015776)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000384816 SCV000381839 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.
Illumina Clinical Services Laboratory,Illumina RCV000292836 SCV000381840 likely benign Hereditary sensory and autonomic neuropathy type II 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000532276 SCV000649408 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Pseudohypoaldosteronism type 2C 2019-06-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 823 of the WNK1 protein (p.His823Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs56015776, ExAC 0.06%) but has not been reported in the literature in individuals with a WNK1-related disease. ClinVar contains an entry for this variant (Variation ID: 310749). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994765 SCV001148508 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing

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