Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| MGZ Medical Genetics Center | RCV002289434 | SCV002580997 | uncertain significance | Ventricular septal defect 3 | 2022-08-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003101669 | SCV003339793 | uncertain significance | Atrial septal defect 7 | 2022-01-16 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 246 of the NKX2-5 protein (p.Asn246Ser). |
| Prevention |
RCV004754873 | SCV005359739 | uncertain significance | NKX2-5-related disorder | 2024-08-08 | no assertion criteria provided | clinical testing | The NKX2-5 c.737A>G variant is predicted to result in the amino acid substitution p.Asn246Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |