Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002624537 | SCV003516864 | uncertain significance | Andersen Tawil syndrome; Short QT syndrome type 3 | 2023-03-22 | criteria provided, single submitter | clinical testing | 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: 2196897). This variant has not been reported in the literature in individuals affected with KCNJ2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 84 of the KCNJ2 protein (p.Met84Thr). |
| ARUP Laboratories, |
RCV003111630 | SCV003800445 | uncertain significance | not provided | 2022-09-12 | criteria provided, single submitter | clinical testing | The KCNJ2 c.251T>C; p.Met84Thr variant (rs1415820562), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The methionine at codon 84 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.824). However, given the lack of clinical and functional data, the significance of the p.Met84Thr variant is uncertain at this time. |
| Ambry Genetics | RCV004070775 | SCV005036617 | uncertain significance | Cardiovascular phenotype | 2023-12-15 | criteria provided, single submitter | clinical testing | The p.M84T variant (also known as c.251T>C), located in coding exon 1 of the KCNJ2 gene, results from a T to C substitution at nucleotide position 251. The methionine at codon 84 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. |