ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.1681C>T (p.Arg561Cys) (rs104894285)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537788 SCV000638113 pathogenic Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive 2016-12-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 561 of the RAG1 protein (p.Arg561Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs104894285, ExAC 0.003%). This variant has been reported as compound heterozygous in multiple individuals affected with SCID or Omenn Syndrome (PMID: 9630231, 11133745, 26596586, and Invitae database). ClinVar contains an entry for this variant (Variation ID: 13148). Experimental studies have shown that another amino acid change at this position, p.Arg561His affects RAG1-RAG2 interaction and causes loss of recombination activity (PMID: 9630231, 24290284), further supporting the functional importance of this residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014030 SCV000034277 pathogenic Histiocytic medullary reticulosis 2001-05-01 no assertion criteria provided literature only
OMIM RCV000014031 SCV000034278 pathogenic Severe combined immunodeficiency, B cell-negative 2001-05-01 no assertion criteria provided literature only

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