ClinVar Miner

Submissions for variant NM_000220.5(KCNJ1):c.634C>T (p.Arg212Ter) (rs201707868)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000406974 SCV000368821 uncertain significance Bartter syndrome, type 2, antenatal 2017-04-27 criteria provided, single submitter clinical testing The KCNJ1 c.634C>T (p.Arg212Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Arg212Ter has been reported in one study in which it was found in one patient with antenatal Bartter syndrome in a compound heterozygous state with a second missense variant (Brochard et al. 2009). This variant was absent from 100 control chromosomes, but is reported at a frequency of 0.00011 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, the p.Arg212Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for antenatal Bartter syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000406974 SCV001134995 pathogenic Bartter syndrome, type 2, antenatal 2019-10-03 criteria provided, single submitter clinical testing A homozygous nonsense variation in exon 2 of the KCNJ1 gene that results in a stop codon and premature truncation of protein at codon 212. The p.Arg212Ter variant has not been reported in the 1000 genomes database and has a minor allele frequency of 0.008% in the ExAC database. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the Arg212Ter variant meets our criteria to be classified as pathogenic.
Johns Hopkins Genomics, Johns Hopkins University RCV000406974 SCV001438393 likely pathogenic Bartter syndrome, type 2, antenatal 2020-09-09 criteria provided, single submitter clinical testing This nonsense variant results in a premature stop codon, likely leading to nonsense-mediated decay and lack of protein production. KCNJ1 c.634C>T has been reported in the compound heterozygous state in an individual presenting with neonatal Bartter syndrome. This variant (rs201707868) is rare (<0.1%) in a large population dataset (gnomAD: 16/280028 total alleles; 0.006%; no homozygotes) and has been reported in ClinVar. We consider this variant to be likely pathogenic.

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