Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001038281 | SCV001201745 | pathogenic | X-linked severe combined immunodeficiency | 2024-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 293 of the IL2RG protein (p.Leu293Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked combined immunodeficiency (XCID) (PMID: 7883965, 12126929). It has also been observed to segregate with disease in related individuals. This variant is also known as Leu271Gln. ClinVar contains an entry for this variant (Variation ID: 10023). 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%. Experimental studies have shown that this missense change affects IL2RG function (PMID: 7973658). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000010706 | SCV000030932 | pathogenic | Combined immunodeficiency, X-linked | 1995-03-01 | no assertion criteria provided | literature only |