ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1041G>A (p.Met347Ile)

gnomAD frequency: 0.00001  dbSNP: rs766318035
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001054685 SCV001219033 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 347 of the RAG2 protein (p.Met347Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs766318035, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001827343 SCV002090477 uncertain significance Histiocytic medullary reticulosis 2020-12-09 no assertion criteria provided clinical testing

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