Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001322934 | SCV001513829 | uncertain significance | Atrial septal defect 7 | 2023-08-03 | 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: 1022958). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. 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 sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 83 of the NKX2-5 protein (p.Ala83Gly). |
Ambry Genetics | RCV002431920 | SCV002741792 | uncertain significance | Cardiovascular phenotype | 2024-01-16 | criteria provided, single submitter | clinical testing | The c.248C>G (p.A83G) alteration is located in exon 1 (coding exon 1) of the NKX2-5 gene. This alteration results from a C to G substitution at nucleotide position 248, causing the alanine (A) at amino acid position 83 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002476516 | SCV002784163 | 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 | 2021-08-17 | criteria provided, single submitter | clinical testing |