ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.2326C>T (p.Arg776Trp) (rs121918572)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000801211 SCV000940977 likely pathogenic Combined cellular and humoral immune defects with granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 776 of the RAG1 protein (p.Arg776Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with severe combined immunodeficiency (SCID) in a family (PMID: 18701881). This variant is also known as C2438T in the literature. ClinVar contains an entry for this variant (Variation ID: 13161). Experimental studies have shown that this missense change impairs V(D)J recombination (PMID: 18701881). The observation of one or more missense substitutions at this codon (p.Arg776Trp and p.Arg776Gln) in affected individuals suggests that this may be a clinically significant residue (PMID: 18701881, 19458910, 17572155). 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.
OMIM RCV000014047 SCV000034294 pathogenic Severe combined immunodeficiency, B cell-negative 2009-02-01 no assertion criteria provided literature only

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