ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.470A>G (p.Lys157Arg)

gnomAD frequency: 0.00006  dbSNP: rs1258478128
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001218779 SCV001390682 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 lysine, which is basic and polar, with arginine, which is basic and polar, at codon 157 of the RAG1 protein (p.Lys157Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 947663). 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 RAG1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV004960566 SCV005491148 uncertain significance Inborn genetic diseases 2024-09-03 criteria provided, single submitter clinical testing The c.470A>G (p.K157R) alteration is located in exon 2 (coding exon 1) of the RAG1 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the lysine (K) at amino acid position 157 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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