ClinVar Miner

Submissions for variant NM_000891.3(KCNJ2):c.752A>G (p.Asn251Ser)

gnomAD frequency: 0.00001  dbSNP: rs1261477163
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523981 SCV000622081 uncertain significance not provided 2017-11-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ2 gene. The N251S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016). This substitution occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, N251S is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Fulgent Genetics, Fulgent Genetics RCV002481741 SCV002780221 uncertain significance Andersen Tawil syndrome; Short QT syndrome type 3; Atrial fibrillation, familial, 9 2021-07-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002525258 SCV003454251 uncertain significance Andersen Tawil syndrome; Short QT syndrome type 3 2024-03-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 251 of the KCNJ2 protein (p.Asn251Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNJ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 453204). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNJ2 protein function with a negative predictive value of 80%. 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.

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