ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.2554A>T (p.Met852Leu)

gnomAD frequency: 0.00004  dbSNP: rs760255456
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001912663 SCV002176842 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-08-14 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 852 of the RAG1 protein (p.Met852Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs760255456, ExAC 0.07%). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. 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: "Possibly 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.
Ambry Genetics RCV004041642 SCV004936067 uncertain significance Inborn genetic diseases 2023-12-15 criteria provided, single submitter clinical testing The c.2554A>T (p.M852L) alteration is located in exon 2 (coding exon 1) of the RAG1 gene. This alteration results from a A to T substitution at nucleotide position 2554, causing the methionine (M) at amino acid position 852 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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