ClinVar Miner

Submissions for variant NM_000890.5(KCNJ5):c.148C>T (p.Arg50Cys)

gnomAD frequency: 0.00002  dbSNP: rs781011854
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001312895 SCV001503366 uncertain significance Long QT syndrome 2025-01-12 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 50 of the KCNJ5 protein (p.Arg50Cys). This variant is present in population databases (rs781011854, gnomAD 0.003%). This missense change has been observed in individual(s) with sudden death (PMID: 26350513). ClinVar contains an entry for this variant (Variation ID: 1014195). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNJ5 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.
AiLife Diagnostics, AiLife Diagnostics RCV002224054 SCV002503247 uncertain significance not provided 2021-12-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395664 SCV002698619 uncertain significance Cardiovascular phenotype 2022-01-07 criteria provided, single submitter clinical testing The p.R50C variant (also known as c.148C>T), located in coding exon 1 of the KCNJ5 gene, results from a C to T substitution at nucleotide position 148. The arginine at codon 50 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a sudden unexplained infant death cohort with limited clinical details (Hertz CL et al. Eur J Hum Genet, 2016 06;24:817-22). 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 RCV002493633 SCV002780160 uncertain significance Long QT syndrome 13; Familial hyperaldosteronism type III 2021-10-17 criteria provided, single submitter clinical testing

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