Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001984543 | SCV002213611 | uncertain significance | Atrial septal defect 7 | 2022-01-19 | 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. 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 C65"). 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 proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 77 of the NKX2-5 protein (p.Pro77Ser). |
| Ambry Genetics | RCV004042122 | SCV005022361 | uncertain significance | Cardiovascular phenotype | 2024-01-22 | criteria provided, single submitter | clinical testing | The p.P77S variant (also known as c.229C>T), located in coding exon 1 of the NKX2-5 gene, results from a C to T substitution at nucleotide position 229. The proline at codon 77 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |