Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001378640 | SCV001576256 | likely pathogenic | X-linked severe combined immunodeficiency | 2020-09-24 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly114 amino acid residue in IL2RG. Other variant(s) that disrupt this residue have been observed in individuals with IL2RG-related conditions (PMID: 8401490), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt IL2RG protein function. This variant has been observed in individual(s) with severe combined immunodeficiency (PMID: 28747913, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with cysteine at codon 114 of the IL2RG protein (p.Gly114Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. |