Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000434919 | SCV000535609 | uncertain significance | not provided | 2023-01-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
| Labcorp Genetics |
RCV000644446 | SCV000766142 | uncertain significance | Atrial septal defect 7 | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 276 of the NKX2-5 protein (p.Ala276Gly). This variant is present in population databases (rs751564052, gnomAD 0.007%). 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: 392351). 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 with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002429460 | SCV002680165 | uncertain significance | Cardiovascular phenotype | 2023-12-30 | criteria provided, single submitter | clinical testing | The p.A276G variant (also known as c.827C>G), located in coding exon 2 of the NKX2-5 gene, results from a C to G substitution at nucleotide position 827. The alanine at codon 276 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV000434919 | SCV003815938 | uncertain significance | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | |
| Center for Genomics, |
RCV003224281 | SCV003920279 | 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 | 2021-03-30 | criteria provided, single submitter | clinical testing | NKX2-5 NM_004387.3 exon 2 p.Ala276Gly (c.827C>G): This variant has not been reported in the literature but is present in 0.006% (7/105084) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-172659720-G-C). This variant is present in ClinVar (Variation ID:392351). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |