ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.1186C>T (p.Arg396Cys) (rs104894289)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000059556 SCV000927913 pathogenic not provided 2018-09-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000014026 SCV000696698 pathogenic Histiocytic medullary reticulosis 2017-03-14 criteria provided, single submitter clinical testing Variant summary: The RAG1 c.1186C>T (p.Arg396Cys) variant located in the homeodomain, DNA binding domain involves the alteration of a conserved nucleotide and is predicted to be damaging by 4/4 in-silico functional prediction tools (SNPs&GO not captured due to low reliability index). This variant is absent in 120606 control chromosomes including broad and large populations of ExAC. This variant has been reported in patients with atypical SCID, Omenn syndrome, or RAG1-related immunodeficiency in compound heterozygous state with other missense variants as well as in a homozygous state including evidence of cosegregation with disease. One functional study shows that this variant leads to severe decrease in VDJ recombination (Lee_2014). Two other missense variants at this codon, R396L and R396H, are also found in patients with RAG1-related phenotypes and lead to severe decrease in VDJ recombination (Lee_2014), suggesting that codon Arg396 is a mutational hot-spot. Taken together, this variant is classified as Pathogenic.
OMIM RCV000014026 SCV000034273 pathogenic Histiocytic medullary reticulosis 1998-05-29 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059556 SCV000091088 not provided not provided no assertion provided not provided

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