Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001236375 | SCV001409098 | likely pathogenic | X-linked severe combined immunodeficiency | 2019-09-27 | criteria provided, single submitter | clinical testing | This variant has been observed in several individuals affected with X-linked severe combined immunodeficiency (PMID: 9633906, 10794431, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 162 of the IL2RG protein (p.Leu162Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |