Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001335330 | SCV001528459 | uncertain significance | Combined immunodeficiency due to partial RAG1 deficiency | 2018-02-09 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Labcorp Genetics |
RCV002547337 | SCV003289668 | uncertain significance | Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 2022-04-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 494 of the RAG1 protein (p.Ile494Val). This variant is present in population databases (rs777216600, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1033034). 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 RAG1 protein function. 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. |