Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Rady Children's Institute for Genomic Medicine, |
RCV001733815 | SCV001984780 | uncertain significance | Combined immunodeficiency, X-linked | criteria provided, single submitter | clinical testing | This variant has not been previously reported or functionally characterized in the literature to our knowledge. However, a different amnio acid change at the same residue (p.Leu162Arg) has been previously reported in multiple individuals with X-linked severe combined immunodeficiency (PMID: 9633906, 10794431). The c.484C>G (p.Leu162Val) variant is located in a well-established functional domain that is intolerant to benign variation (PMID: 7668284). It is absent from the gnomAD population database and thus is presumed to be rare. The c.484C>G (p.Leu162Val) variant is predicted by multiple in silico tools to have a benign effect on protein function. Based on the available evidence, the c.484C>G (p.Leu162Val) variant is classified as Variant of Uncertain Significance. | |
| Labcorp Genetics |
RCV002032743 | SCV002241701 | uncertain significance | X-linked severe combined immunodeficiency | 2022-07-05 | criteria provided, single submitter | clinical testing | 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 IL2RG protein function. ClinVar contains an entry for this variant (Variation ID: 1301872). This variant has not been reported in the literature in individuals affected with IL2RG-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 162 of the IL2RG protein (p.Leu162Val). This variant disrupts the p.Leu162 amino acid residue in IL2RG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9633906, 10794431; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317521 | SCV004020496 | uncertain significance | not specified | 2023-06-30 | criteria provided, single submitter | clinical testing |