ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.997T>C (p.Tyr333His)

gnomAD frequency: 0.00001  dbSNP: rs1041695603
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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 RCV000798507 SCV000938126 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-04-09 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 333 of the RAG1 protein (p.Tyr333His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 644561). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
New York Genome Center RCV001839023 SCV002099210 uncertain significance Combined immunodeficiency due to partial RAG1 deficiency; Combined immunodeficiency with skin granulomas; Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-03-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV003279074 SCV003959981 uncertain significance Inborn genetic diseases 2023-05-04 criteria provided, single submitter clinical testing The c.997T>C (p.Y333H) alteration is located in exon 2 (coding exon 1) of the RAG1 gene. This alteration results from a T to C substitution at nucleotide position 997, causing the tyrosine (Y) at amino acid position 333 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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