Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003619568 | SCV004517470 | uncertain significance | Atrial septal defect 7 | 2023-09-06 | 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. This variant is present in population databases (no rsID available, gnomAD 0.02%). 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. This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 234 of the NKX2-5 protein (p.Ser234Trp). |
| Ambry Genetics | RCV004374062 | SCV005022428 | uncertain significance | Cardiovascular phenotype | 2023-10-24 | criteria provided, single submitter | clinical testing | The p.S234W variant (also known as c.701C>G), located in coding exon 2 of the NKX2-5 gene, results from a C to G substitution at nucleotide position 701. The serine at codon 234 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is not 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. |