ClinVar Miner

Submissions for variant NM_000448.2(RAG1):c.1331C>T (p.Ala444Val) (rs199474685)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559478 SCV000638112 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2017-03-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 444 of the RAG1 protein (p.Ala444Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs199474685, ExAC 0.006%). This variant has been observed as homozygous or co-occurring with a second RAG1 variant in several individuals affected with various forms of primary immunodeficiency with evidence of disease co-segregation in a family (PMID: 11133745, 23085344, 24290284, 26596586, Invitae). ClinVar contains an entry for this variant (Variation ID: 68681). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000059562 SCV001248253 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059562 SCV000091094 not provided not provided no assertion provided not provided

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.