Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000619357 | SCV000736271 | uncertain significance | Cardiovascular phenotype | 2022-04-14 | criteria provided, single submitter | clinical testing | The p.T402M variant (also known as c.1205C>T), located in coding exon 1 of the KCNJ2 gene, results from a C to T substitution at nucleotide position 1205. The threonine at codon 402 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000627126 | SCV000747930 | uncertain significance | not specified | 2017-04-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000698640 | SCV000827320 | uncertain significance | Andersen Tawil syndrome; Short QT syndrome type 3 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 402 of the KCNJ2 protein (p.Thr402Met). This variant is present in population databases (rs759070406, gnomAD 0.02%). 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: 518798). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |