ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.1798del (p.Glu600fs)

dbSNP: rs2133296385
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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 RCV001389760 SCV001591213 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2020-09-23 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with RAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the RAG1 gene (p.Glu600Serfs*9). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 444 amino acids of the RAG1 protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the RAG1 protein. Other variant(s) that disrupt this region (p.Trp959*) have been determined to be pathogenic (PMID: 24290284, 11133745, 24406074). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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