Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003860078 | SCV004661182 | uncertain significance | Atrial septal defect 7 | 2023-09-25 | 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. 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. This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 288 of the NKX2-5 protein (p.Ala288Thr). |
| Ambry Genetics | RCV004369516 | SCV005022384 | uncertain significance | Cardiovascular phenotype | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.A288T variant (also known as c.862G>A), located in coding exon 2 of the NKX2-5 gene, results from a G to A substitution at nucleotide position 862. The alanine at codon 288 is replaced by threonine, an amino acid with similar properties. This amino acid position is 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. |