Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617167 | SCV000737200 | uncertain significance | Cardiovascular phenotype | 2021-11-18 | criteria provided, single submitter | clinical testing | The p.G296D variant (also known as c.887G>A), located in coding exon 2 of the NKX2-5 gene, results from a G to A substitution at nucleotide position 887. The glycine at codon 296 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003619712 | SCV004526447 | uncertain significance | Atrial septal defect 7 | 2023-07-19 | 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 NKX2-5 protein function. ClinVar contains an entry for this variant (Variation ID: 519139). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (rs373421818, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 296 of the NKX2-5 protein (p.Gly296Asp). |