Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001065033 | SCV001229971 | uncertain significance | Atrial septal defect 7 | 2022-03-09 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 859023). This missense change has been observed in individual(s) with clinical features of NKX2-5-related conditions (PMID: 26014430). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 237 of the NKX2-5 protein (p.Tyr237His). |
| Ambry Genetics | RCV003160536 | SCV003891848 | uncertain significance | Cardiovascular phenotype | 2023-01-09 | criteria provided, single submitter | clinical testing | The p.Y237H variant (also known as c.709T>C), located in coding exon 2 of the NKX2-5 gene, results from a T to C substitution at nucleotide position 709. The tyrosine at codon 237 is replaced by histidine, an amino acid with similar properties. This alteration has been reported in an individual with an atrial septal defect; however, an additional alteration in NKX2-5 was also identified (El Malti R et al. Eur J Hum Genet, 2016 Feb;24:228-36). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |