Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000540219 | SCV000644786 | uncertain significance | Atrial septal defect 7 | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 315 of the NKX2-5 protein (p.Val315Leu). This variant is present in population databases (rs201249977, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with tetralogy of Fallot (PMID: 19948535). ClinVar contains an entry for this variant (Variation ID: 468249). 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%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on NKX2-5 function (PMID: 19948535, 21677783). 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. |
| Mendelics | RCV000540219 | SCV001137024 | likely benign | Atrial septal defect 7 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000998493 | SCV001955634 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001727746 | SCV001975984 | benign | not specified | no assertion criteria provided | clinical testing |