Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000002035 | SCV001220995 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 304 of the ADA protein (p.Leu304Arg). This variant is present in population databases (rs199422327, gnomAD 0.008%). This missense change has been observed in individual(s) with severe combined immunodeficiency (PMID: 46025, 1284479, 17185467). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1006T>G. ClinVar contains an entry for this variant (Variation ID: 1958). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ADA protein function. Experimental studies have shown that this missense change affects ADA function (PMID: 3007108). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV000002035 | SCV002060121 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2021-11-10 | criteria provided, single submitter | clinical testing | NM_000022.2(ADA):c.911T>G(L304R) is a missense variant classified as likely pathogenic in the context of adenosine deaminase deficiency. L304R has been observed in cases with relevant disease (PMID: 17185467, 1346349). Functional assessments of this variant are available in the literature (PMID: 3007108). L304R has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, NM_000022.2(ADA):c.911T>G(L304R) is a missense variant that has functional support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Baylor Genetics | RCV000002035 | SCV004213534 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2023-03-24 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000002035 | SCV000022193 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 1986-01-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000002035 | SCV002095301 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2021-03-05 | no assertion criteria provided | clinical testing |