ClinVar Miner

Submissions for variant NM_000891.3(KCNJ2):c.973C>T (p.Arg325Cys)

gnomAD frequency: 0.00007  dbSNP: rs202067116
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170995 SCV000223558 uncertain significance not provided 2019-09-18 criteria provided, single submitter clinical testing Has been reported in one individual with LQTS; however this individual also harbored a pathogenic variant in a second cardiac gene related to LQTS (Burns et al., 2016); Also reported as a variant of uncertain significant in a adult male with sudden cardiac arrest and no prior cardiac phenotype; additional information, such segregation or functional studies were not specified in this report (Asatryan et al., 2019); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27920829, 30975432, 31737537)
Blueprint Genetics RCV000208475 SCV000263988 uncertain significance Ventricular fibrillation 2015-05-22 criteria provided, single submitter clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000496264 SCV000588150 uncertain significance Andersen Tawil syndrome 2017-03-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000816436 SCV000956945 uncertain significance Andersen Tawil syndrome; Short QT syndrome type 3 2023-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 325 of the KCNJ2 protein (p.Arg325Cys). This variant is present in population databases (rs202067116, gnomAD 0.02%). This missense change has been observed in individual(s) with arrhythmogenic disorders and/or long QT syndrome (PMID: 27920829, 30975432, 31737537). ClinVar contains an entry for this variant (Variation ID: 190821). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNJ2 protein function. 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.
Ambry Genetics RCV002372065 SCV002692753 benign Cardiovascular phenotype 2022-09-27 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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