ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.123C>G (p.Cys41Trp)

dbSNP: rs121917895
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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 RCV000681574 SCV000693922 likely pathogenic Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive; Recombinase activating gene 2 deficiency; Inborn error of immunity 2018-03-06 criteria provided, single submitter research
Invitae RCV001851843 SCV002228430 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-02-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RAG2 function (PMID: 9630231, 29772310). 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. ClinVar contains an entry for this variant (Variation ID: 13131). This missense change has been observed in individual(s) with severe combined immunodeficiency (PMID: 9630231, 28769923, 29772310). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 41 of the RAG2 protein (p.Cys41Trp).
OMIM RCV000014012 SCV000034259 pathogenic Histiocytic medullary reticulosis 1998-05-29 no assertion criteria provided literature only

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