ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.419A>G (p.His140Arg)

dbSNP: rs1335036396
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001046638 SCV001210548 likely pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 140 of the RAG2 protein (p.His140Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of severe combined immunodeficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 843920). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAG2 protein function with a positive predictive value of 95%. 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.
Natera, Inc. RCV001832439 SCV002087160 uncertain significance Histiocytic medullary reticulosis 2021-08-05 no assertion criteria provided clinical testing

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