ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.2006A>G (p.Glu669Gly)

dbSNP: rs199474689
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003764744 SCV004570842 likely pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-05-22 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 669 of the RAG1 protein (p.Glu669Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Omenn syndrome (PMID: 11133745, 24144642). ClinVar contains an entry for this variant (Variation ID: 68688). 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. This variant disrupts the p.Glu669 amino acid residue in RAG1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24144642, 26476733, 28747913, 32655540). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
UniProtKB/Swiss-Prot RCV000059569 SCV000091101 not provided not provided no assertion provided not provided

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