Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001980148 | SCV002237328 | uncertain significance | Atrial septal defect 7 | 2021-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 156 of the NKX2-5 protein (p.Arg156Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV002331515 | SCV002634386 | uncertain significance | Cardiovascular phenotype | 2021-07-12 | criteria provided, single submitter | clinical testing | The p.R156C variant (also known as c.466C>T), located in coding exon 2 of the NKX2-5 gene, results from a C to T substitution at nucleotide position 466. The arginine at codon 156 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |