Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001242919 | SCV001416041 | pathogenic | Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 2023-06-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RAG1 protein in which other variant(s) (p.Lys992Glu) have been determined to be pathogenic (PMID: 11313270, 18442948, 24290284). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 967900). This premature translational stop signal has been observed in individuals with clinical features of severe combined immunodeficiency (PMID: 11133745, 24290284, 24406074). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp959*) in the RAG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acid(s) of the RAG1 protein. |