Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000702882 | SCV000831754 | uncertain significance | Kostmann syndrome | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 16 of the HAX1 protein (p.Pro16Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs763746492, ExAC 0.03%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Center for Genomics, |
RCV000702882 | SCV003920024 | uncertain significance | Kostmann syndrome | 2022-10-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.02% [7/34568]; https://gnomad.broadinstitute.org/variant/1-154245245-C-T?dataset=gnomad_r2_1), and in ClinVar (Variation ID: 579564). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Ambry Genetics | RCV004972889 | SCV005596170 | uncertain significance | Inborn genetic diseases | 2024-11-26 | criteria provided, single submitter | clinical testing | The p.P16S variant (also known as c.46C>T), located in coding exon 1 of the HAX1 gene, results from a C to T substitution at nucleotide position 46. The proline at codon 16 is replaced by serine, 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. |
Natera, |
RCV000702882 | SCV002085814 | uncertain significance | Kostmann syndrome | 2019-10-28 | no assertion criteria provided | clinical testing |