Submissions for variant NM_000448.3(RAG1):c.2147G>A (p.Arg716Gln)

dbSNP: rs1064793248

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483831	SCV000565474	likely pathogenic	not provided	2014-08-13	criteria provided, single submitter	clinical testing	To our knowledge, the R716Q variant has neither been published as pathogenic, nor reported as a benign polymorphism. This variant was not observed in approximately 6500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. R716Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same and nearby residues (R716W, G709D, E722K) have been reported in the Human Gene Mutation Database in association with RAG1-deficiency disorders (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this is a strong candidate for a pathogenic variant; however, the possibility that it is a benign variant cannot be excluded.
Baylor Genetics	RCV004568146	SCV005054055	likely pathogenic	Combined immunodeficiency due to partial RAG1 deficiency	2024-02-20	criteria provided, single submitter	clinical testing
Pediatric Intensive Care Unit, Hunan Children's Hospital	RCV002466255	SCV002756461	uncertain significance	Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive		no assertion criteria provided	clinical testing