ClinVar Miner

Submissions for variant NM_018979.4(WNK1):c.2140-2568C>T (rs111033591)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480631 SCV000568662 pathogenic not provided 2017-02-13 criteria provided, single submitter clinical testing The R1076X nonsense variant in the WNK1 gene has been previously reported, using alternative nomenclature of R290X, as a homozygous variant in a child with HSAN2 (Roddier et al., 2005). The R1076X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, R1076X is interpreted to be a pathogenic variant.
Invitae RCV000822434 SCV000963235 pathogenic Hereditary sensory and autonomic neuropathy type IIA; Pseudohypoaldosteronism type 2C 2018-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1076*) in the WNK1 gene. It is expected to result in an absent or disrupted protein product. The WNK1 gene has multiple clinically relevant transcripts. The p.Arg1076* variant occurs in alternate transcript  NM_213655.4, which corresponds to position c.2140-2568C>T in NM_018979.3, the primary transcript listed in the Methods. This variant is present in population databases (rs111033591, ExAC 0.01%). This variant has been observed in the homozygous state in an individual affected with autosomal recessive hereditary sensory and autonomic neuropathy (PMID: 15911806). This variant is also referred to as p.Arg290X in the literature. ClinVar contains an entry for this variant (Variation ID: 5168). Loss-of-function variants in WNK1 are known to be pathogenic (PMID: 22910560). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005475 SCV000025657 pathogenic Hereditary sensory and autonomic neuropathy type IIA 2005-05-24 no assertion criteria provided literature only

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