ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.671G>C (p.Arg224Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003510334 SCV004331162 likely pathogenic X-linked severe combined immunodeficiency 2023-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 224 of the IL2RG protein (p.Arg224Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with severe combined immunodeficiency (Invitae). 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 with a positive predictive value of 80%. This variant disrupts the p.Arg224 amino acid residue in IL2RG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9049783, 9058718, 9633906, 10792291, 21184155, 28747913). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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