Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001344953 | SCV001539039 | uncertain significance | Atrial septal defect 7 | 2021-06-16 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NKX2-5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with arginine at codon 185 of the NKX2-5 protein (p.Trp185Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. |
| Ambry Genetics | RCV003284235 | SCV004006443 | uncertain significance | Cardiovascular phenotype | 2023-04-05 | criteria provided, single submitter | clinical testing | The p.W185R variant (also known as c.553T>C), located in coding exon 2 of the NKX2-5 gene, results from a T to C substitution at nucleotide position 553. The tryptophan at codon 185 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly 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. |