Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000471990 | SCV000551865 | uncertain significance | Atrial septal defect 7 | 2023-06-17 | 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: 410970). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (rs770192204, gnomAD 0.03%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 236 of the NKX2-5 protein (p.Pro236Thr). |
| Ambry Genetics | RCV004022858 | SCV003745330 | uncertain significance | Cardiovascular phenotype | 2021-09-16 | criteria provided, single submitter | clinical testing | The c.706C>A (p.P236T) alteration is located in exon 2 (coding exon 2) of the NKX2-5 gene. This alteration results from a C to A substitution at nucleotide position 706, causing the proline (P) at amino acid position 236 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |