Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000620703 | SCV000737640 | uncertain significance | Cardiovascular phenotype | 2016-07-12 | criteria provided, single submitter | clinical testing | The p.H319R variant (also known as c.956A>G), located in coding exon 2 of the NKX2-5 gene, results from an A to G substitution at nucleotide position 956. The histidine at codon 319 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly 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 variant remains unclear. |
| Gene |
RCV001756005 | SCV001986657 | uncertain significance | not provided | 2018-10-01 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server); Reported as a variant of uncertain significance in ClinVar but additional evidence is not available (SCV000737640.1; Landrum et al., 2016) |
| Labcorp Genetics |
RCV003619713 | SCV004507739 | uncertain significance | Atrial septal defect 7 | 2023-07-17 | 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. 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. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 319 of the NKX2-5 protein (p.His319Arg). This variant is present in population databases (no rsID available, 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: 519292). |