ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.541T>C (p.Cys181Arg)

gnomAD frequency: 0.00001  dbSNP: rs1564996998
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000705346 SCV000834338 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-02-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 181 of the RAG2 protein (p.Cys181Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581504). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAG2 protein function. 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.
Ambry Genetics RCV004958045 SCV005491154 uncertain significance Inborn genetic diseases 2024-08-26 criteria provided, single submitter clinical testing The c.541T>C (p.C181R) alteration is located in exon 2 (coding exon 1) of the RAG2 gene. This alteration results from a T to C substitution at nucleotide position 541, causing the cysteine (C) at amino acid position 181 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001830558 SCV002087127 uncertain significance Histiocytic medullary reticulosis 2020-03-13 no assertion criteria provided clinical testing

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