Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001925447 | SCV002168617 | uncertain significance | Atrial septal defect 7 | 2023-05-09 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt NKX2-5 protein function. ClinVar contains an entry for this variant (Variation ID: 1403770). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 275 of the NKX2-5 protein (p.Pro275Ser). |
Gene |
RCV003225200 | SCV003921550 | uncertain significance | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |