ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.221G>T (p.Gly74Val)

gnomAD frequency: 0.00009  dbSNP: rs199422328
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000002054 SCV000953974 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-06-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 74 of the ADA protein (p.Gly74Val). This variant is present in population databases (rs199422328, gnomAD 0.03%). This missense change has been observed in individual(s) with adenosine deaminase deficiency (PMID: 8614422, 27129325; Invitae). ClinVar contains an entry for this variant (Variation ID: 1977). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ADA function (PMID: 8614422, 9758612). This variant disrupts the p.Gly74 amino acid residue in ADA. Other variant(s) that disrupt this residue have been observed in individuals with ADA-related conditions (PMID: 30290665), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000002054 SCV004213378 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-03-23 criteria provided, single submitter clinical testing
OMIM RCV000002054 SCV000022212 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 1996-05-23 no assertion criteria provided literature only
Natera, Inc. RCV000002054 SCV002095334 likely pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2020-08-12 no assertion criteria provided clinical testing

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.