Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171011 | SCV000223575 | uncertain significance | not provided | 2016-08-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NKX2-5 gene. The R197P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R197P variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R197P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. |
| Labcorp Genetics |
RCV001852050 | SCV002163796 | uncertain significance | Atrial septal defect 7 | 2023-06-09 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NKX2-5 protein function. ClinVar contains an entry for this variant (Variation ID: 190835). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 197 of the NKX2-5 protein (p.Arg197Pro). |
| Ai |
RCV000171011 | SCV002501925 | uncertain significance | not provided | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002354420 | SCV002653726 | uncertain significance | Cardiovascular phenotype | 2021-01-22 | criteria provided, single submitter | clinical testing | The p.R197P variant (also known as c.590G>C), located in coding exon 2 of the NKX2-5 gene, results from a G to C substitution at nucleotide position 590. The arginine at codon 197 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002492707 | SCV002792993 | uncertain significance | Atrial septal defect 7; Conotruncal heart malformations; Hypothyroidism, congenital, nongoitrous, 5; Tetralogy of Fallot; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 | 2021-08-10 | criteria provided, single submitter | clinical testing |