Submissions for variant NM_000448.3(RAG1):c.206del (p.Ala69fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003779475	SCV004603859	pathogenic	Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala69Valfs*13) in the RAG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 975 amino acid(s) of the RAG1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. 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. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV004573298	SCV005054058	likely pathogenic	Combined immunodeficiency due to partial RAG1 deficiency	2024-01-23	criteria provided, single submitter	clinical testing