ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.983G>A (p.Cys328Tyr) (rs121918571)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820844 SCV000961575 pathogenic Combined cellular and humoral immune defects with granulomas; Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive 2018-12-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 328 of the RAG1 protein (p.Cys328Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs121918571, ExAC 0.01%). This variant has been observed in individuals affected with Omenn syndrome and with clinical features of severe combined immunodeficiency (PMID: 11133745, 17572155, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 13160). This variant has been reported to affect RAG1 protein function (PMID: 18056378, 24290284). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014046 SCV000034293 pathogenic Histiocytic medullary reticulosis 2007-12-15 no assertion criteria provided literature only

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