Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003086482 | SCV003481237 | uncertain significance | Kostmann syndrome | 2023-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 235 of the HAX1 protein (p.Arg235Trp). 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 HAX1 protein function. ClinVar contains an entry for this variant (Variation ID: 2167517). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. This variant is present in population databases (rs373783109, gnomAD 0.01%). |
| Ambry Genetics | RCV004978592 | SCV005596155 | uncertain significance | Inborn genetic diseases | 2024-11-23 | criteria provided, single submitter | clinical testing | The p.R235W variant (also known as c.703C>T), located in coding exon 6 of the HAX1 gene, results from a C to T substitution at nucleotide position 703. The arginine at codon 235 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |