ClinVar Miner

Submissions for variant NM_000891.3(KCNJ2):c.236T>C (p.Ile79Thr)

gnomAD frequency: 0.00002  dbSNP: rs786205813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170975 SCV000223538 uncertain significance not provided 2022-08-19 criteria provided, single submitter clinical testing Published functional studies have shown that I79T is associated with sensitivity to inhibition with carbon monoxide when present with the L222I variant and is associated with sensitivity to inhibition with phorbol 12-myristate 13-acetate (PMA) (Zhu et al., 1999; Liang et al., 2014). However, these results are not sufficient to establish a damaging effect.; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10206975, 31589614, 25118981)
Mendelics RCV000170975 SCV001135101 uncertain significance not provided 2022-03-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852048 SCV002219726 uncertain significance Andersen Tawil syndrome; Short QT syndrome type 3 2023-04-15 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 79 of the KCNJ2 protein (p.Ile79Thr). This variant has not been reported in the literature in individuals affected with KCNJ2-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 190809).
Ambry Genetics RCV004020039 SCV005036830 uncertain significance Cardiovascular phenotype 2023-11-22 criteria provided, single submitter clinical testing The p.I79T variant (also known as c.236T>C), located in coding exon 1 of the KCNJ2 gene, results from a T to C substitution at nucleotide position 236. The isoleucine at codon 79 is replaced by threonine, an amino acid with similar properties. 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.

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