Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587249 | SCV000698409 | uncertain significance | not provided | 2017-07-18 | criteria provided, single submitter | clinical testing | Variant summary: The NKX2-5 c.662C>T (p.Pro221Leu) variant involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome. However, no functional studies supporting these predictions were published at the time of evaluation. The variant is located outside of any known domain or repeat (InterPro). This variant is absent in 95726 control chromosomes (ExAC). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Labcorp Genetics |
RCV002530931 | SCV003216731 | uncertain significance | Atrial septal defect 7 | 2023-08-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 221 of the NKX2-5 protein (p.Pro221Leu). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. 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) 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. ClinVar contains an entry for this variant (Variation ID: 496237). |