Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001963931 | SCV002254679 | uncertain significance | Kostmann syndrome | 2022-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 246 of the HAX1 protein (p.Asp246His). This variant is present in population databases (rs375477111, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV004989006 | SCV005596136 | uncertain significance | Inborn genetic diseases | 2024-10-17 | criteria provided, single submitter | clinical testing | The p.D246H variant (also known as c.736G>C), located in coding exon 6 of the HAX1 gene, results from a G to C substitution at nucleotide position 736. The aspartic acid at codon 246 is replaced by histidine, an amino acid with similar 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. |