ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1375A>C (p.Met459Leu)

dbSNP: rs1204766339
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pediatric Immunology Service, The Chaim Sheba Medical Center at Tel HaShomer RCV000681600 SCV000693948 likely pathogenic Combined immunodeficiency with skin granulomas; Histiocytic medullary reticulosis; Atypical severe combined immunodeficiency due to complete RAG1/2 deficiency; Recombinase activating gene 2 deficiency; Inborn error of immunity 2018-03-06 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001378887 SCV001576576 likely pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2020-05-27 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported to affect RAG2 protein function (PMID: 22841008, 29772310, 26692406). This variant has been observed to be homozygous or in combination with another RAG2 variant in individuals affected with Omenn syndrome, combined immunodeficiency with granulomatous disease and/or autoimmunity (CID-G/AI) and hyper-IgM syndrome (PMID: 22841008, 26457731). ClinVar contains an entry for this variant (Variation ID: 496632). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 459 of the RAG2 protein (p.Met459Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine.
Natera, Inc. RCV001834862 SCV002090400 likely pathogenic Histiocytic medullary reticulosis 2020-04-23 no assertion criteria provided clinical testing

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