Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000215113 | SCV000271204 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2015-11-09 | criteria provided, single submitter | clinical testing | The p.Arg235Gln variant in ADA has been reported in 3 individuals with SCID due to adenosine deaminase deficiency, confirmed by decreased ADA enzyme activity in patient cells (Ariga 2001a, Baffelli 2015). All of these individuals were compo und heterozygous and two of them had a second ADA variant predicted to cause los s of function of the gene on the other allele. The p.Arg235Gln variant was absen t from large population studies. Computational prediction tools and conservation analyses suggest that the variant may impact the protein, though this informati on is not predictive enough to determine pathogenicity. Furthermore, in vitro fu nctional studies provide some evidence that this variant impacts protein functio n (Ariga 2001b), although these types of assays may not accurately represent bio logical function. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |
| Counsyl | RCV000215113 | SCV000794032 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2017-09-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000215113 | SCV000813414 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2024-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 235 of the ADA protein (p.Arg235Gln). This variant is present in population databases (rs79281338, gnomAD 0.003%). This missense change has been observed in individual(s) with adenosine deaminase deficiency (PMID: 11313286, 26376800). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 228244). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ADA protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ADA function (PMID: 11160213). This variant disrupts the p.Arg235 amino acid residue in ADA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21624848, 26255240, 26376800; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000215113 | SCV001977498 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000215113 | SCV004216770 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2024-02-13 | criteria provided, single submitter | clinical testing |