ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.2923C>T (p.Arg975Trp) (rs121918570)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820053 SCV000960746 uncertain significance Combined cellular and humoral immune defects with granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 975 of the RAG1 protein (p.Arg975Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121918570, ExAC 0.003%). This variant has been observed in individuals affected with granulomatous disease and Omenn syndrome (PMID: 18463379, 24290284, 19064334). ClinVar contains an entry for this variant (Variation ID: 13159). This variant has been reported to affect RAG1 protein function (PMID: 24290284). This variant disrupts the Arg975 amino acid residue in RAG1. Other variant(s) that disrupt this residue have been observed in individuals with RAG1-related conditions (PMID: 24290284, 27484032, 11133745), which suggests that this may be a clinically significant amino acid residue. 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.
OMIM RCV000014045 SCV000034292 pathogenic Combined cellular and humoral immune defects with granulomas 2008-05-08 no assertion criteria provided literature only

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