ClinVar Miner

Submissions for variant NM_000891.3(KCNJ2):c.974G>A (p.Arg325His)

gnomAD frequency: 0.00001  dbSNP: rs1555604000
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498871 SCV000589379 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ2 gene. The R325H variant has been reported in at least one patient with LQTS (Chang et al., 2014); however additional clinical details and segregation information were not provided. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R325H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Ambry Genetics RCV002383953 SCV002693426 uncertain significance Cardiovascular phenotype 2024-01-19 criteria provided, single submitter clinical testing The p.R325H variant (also known as c.974G>A), located in coding exon 1 of the KCNJ2 gene, results from a G to A substitution at nucleotide position 974. The arginine at codon 325 is replaced by histidine, an amino acid with highly similar properties. This variant was detected as heterozygous in one individual from a sensorineural hearing loss cohort who had a borderline QTc interval and an additional SCN5A variant also detected (Chang RK et al. J. Pediatr., 2014 Mar;164:590-5.e1-3). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002475984 SCV002789142 uncertain significance Andersen Tawil syndrome; Short QT syndrome type 3; Atrial fibrillation, familial, 9 2021-11-04 criteria provided, single submitter clinical testing

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