ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.2210G>A (p.Arg737His)

gnomAD frequency: 0.00002  dbSNP: rs104894286
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV001027614 SCV001190186 likely pathogenic Inherited Immunodeficiency Diseases 2019-01-01 criteria provided, single submitter research
CeGaT Center for Human Genetics Tuebingen RCV001091955 SCV001248258 pathogenic not provided 2019-06-01 criteria provided, single submitter clinical testing
Invitae RCV001389160 SCV001590426 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 737 of the RAG1 protein (p.Arg737His). This variant is present in population databases (rs104894286, gnomAD 0.02%). This missense change has been observed in individual(s) with severe combined immunodeficiency and Omenn syndrome (PMID: 9630231, 17572155, 28109013, 30290665, 30858051). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as G2322A and c.2322G>A. ClinVar contains an entry for this variant (Variation ID: 13149). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAG1 protein function. Experimental studies have shown that this missense change affects RAG1 function (PMID: 9630231). For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003227600 SCV003924311 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-05-08 criteria provided, single submitter research
Baylor Genetics RCV003473093 SCV004200479 pathogenic Combined immunodeficiency due to partial RAG1 deficiency 2024-03-27 criteria provided, single submitter clinical testing
OMIM RCV000014032 SCV000034279 pathogenic Histiocytic medullary reticulosis 1998-05-29 no assertion criteria provided literature only

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