ClinVar Miner

Submissions for variant NM_000890.5(KCNJ5):c.994C>T (p.Arg332Ter)

gnomAD frequency: 0.00005  dbSNP: rs746985291
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001363248 SCV001559352 uncertain significance Long QT syndrome 2024-10-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg332*) in the KCNJ5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 88 amino acid(s) of the KCNJ5 protein. This variant is present in population databases (rs746985291, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with KCNJ5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1054696). 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.
Fulgent Genetics, Fulgent Genetics RCV002504596 SCV002815902 uncertain significance Long QT syndrome 13; Familial hyperaldosteronism type III 2024-04-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV004619669 SCV005124728 uncertain significance Cardiovascular phenotype 2024-03-29 criteria provided, single submitter clinical testing The p.R332* variant (also known as c.994C>T), located in coding exon 2 of the KCNJ5 gene, results from a C to T substitution at nucleotide position 994. This changes the amino acid from an arginine to a stop codon within coding exon 2. Based on data from gnomAD, the frequency for this variant is above the maximum credible frequency for a hyperaldosteronism disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). This alteration is expected to result in protein truncation. However, loss of function of KCNJ5 has not been established as a mechanism of disease. Based on the available evidence, the clinical significance of this alteration remains unclear for long QT syndrome; however, it is unlikely to be causative of hyperaldosteronism.

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