Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001241157 | SCV001414153 | uncertain significance | Kostmann syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 253 of the HAX1 protein (p.Pro253Thr). This variant is present in population databases (rs149721308, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 966471). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003353254 | SCV004064979 | uncertain significance | Inborn genetic diseases | 2024-10-02 | criteria provided, single submitter | clinical testing | The p.P253T variant (also known as c.757C>A), located in coding exon 7 of the HAX1 gene, results from a C to A substitution at nucleotide position 757. The proline at codon 253 is replaced by threonine, an amino acid with highly 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. |
Ce |
RCV003883587 | SCV004701756 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | HAX1: PM2, BP4 |
Natera, |
RCV001241157 | SCV002086440 | uncertain significance | Kostmann syndrome | 2020-02-13 | no assertion criteria provided | clinical testing |