Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002419126 | SCV002681687 | uncertain significance | Cardiovascular phenotype | 2019-07-05 | criteria provided, single submitter | clinical testing | The p.G267R variant (also known as c.799G>C), located in coding exon 2 of the NKX2-5 gene, results from a G to C substitution at nucleotide position 799. The glycine at codon 267 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available 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 alteration remains unclear. |
| Labcorp Genetics |
RCV003099808 | SCV003015796 | uncertain significance | Atrial septal defect 7 | 2022-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 267 of the NKX2-5 protein (p.Gly267Arg). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (rs780688010, gnomAD 0.02%). |