Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001960073 | SCV002214734 | uncertain significance | Atrial septal defect 7 | 2021-04-08 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 asparagine with threonine at codon 291 of the NKX2-5 protein (p.Asn291Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. |
| Ambry Genetics | RCV002370558 | SCV002685278 | uncertain significance | Cardiovascular phenotype | 2019-04-16 | criteria provided, single submitter | clinical testing | The p.N291T variant (also known as c.872A>C), located in coding exon 2 of the NKX2-5 gene, results from an A to C substitution at nucleotide position 872. The asparagine at codon 291 is replaced by threonine, an amino acid with similar properties. A deletion of this amino acid was detected in a congenital heart defect cohort (McElhinney DB. J. Am. Coll. Cardiol.. 2003;42(9):1650-5). This amino acid position is 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. |