Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001934418 | SCV002208997 | uncertain significance | Atrial septal defect 7 | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 124 of the NKX2-5 protein (p.Lys124Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1439076). 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. 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. |
| Fulgent Genetics, |
RCV002484696 | SCV002786481 | uncertain significance | Atrial septal defect 7; Conotruncal heart malformations; Hypothyroidism, congenital, nongoitrous, 5; Tetralogy of Fallot; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 | 2022-02-22 | criteria provided, single submitter | clinical testing |