ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.1467G>C (p.Arg489Ser)

gnomAD frequency: 0.00001  dbSNP: rs1270133689
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000761770 SCV000891962 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001039344 SCV001202874 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2019-01-16 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 489 of the RAG1 protein (p.Arg489Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000761770 SCV002047720 uncertain significance not provided 2021-06-11 criteria provided, single submitter clinical testing The RAG1 c.1467G>C; p.Arg489Ser variant (rs1270133689), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 623769). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 489is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.645). Due to limited information, the clinical significance of the p.Arg489Ser variant is uncertain at this time.

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