ClinVar Miner

Submissions for variant NM_000448.3(RAG1):c.1256A>G (p.Lys419Arg)

gnomAD frequency: 0.00002  dbSNP: rs780974569
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795280 SCV000934732 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-08-28 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 419 of the RAG1 protein (p.Lys419Arg). This variant is present in population databases (rs780974569, gnomAD 0.004%). 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: 641925). 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"). 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 RCV003243301 SCV003950330 uncertain significance Inborn genetic diseases 2023-05-31 criteria provided, single submitter clinical testing The c.1256A>G (p.K419R) 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 1256, causing the lysine (K) at amino acid position 419 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.