Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001066161 | SCV001231162 | uncertain significance | Kostmann syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 175 of the HAX1 protein (p.Met175Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs747655324, ExAC 0.01%). 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. 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. |
Natera, |
RCV001066161 | SCV002085831 | uncertain significance | Kostmann syndrome | 2021-08-25 | no assertion criteria provided | clinical testing |