Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001997483 | SCV002230217 | uncertain significance | Atrial septal defect 7 | 2021-07-25 | 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. 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 (rs781370140, ExAC 0.002%). This sequence change replaces valine with methionine at codon 243 of the NKX2-5 protein (p.Val243Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. |
| Ambry Genetics | RCV004043914 | SCV005022429 | uncertain significance | Cardiovascular phenotype | 2023-12-31 | criteria provided, single submitter | clinical testing | The p.V243M variant (also known as c.727G>A), located in coding exon 2 of the NKX2-5 gene, results from a G to A substitution at nucleotide position 727. The valine at codon 243 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |