ClinVar Miner

Submissions for variant NM_000022.2(ADA):c.986C>T (rs121908715)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000002036 SCV000792636 likely pathogenic Severe combined immunodeficiency due to ADA deficiency 2017-07-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000002036 SCV000894218 pathogenic Severe combined immunodeficiency due to ADA deficiency 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000373062 SCV000329052 pathogenic not provided 2017-04-14 criteria provided, single submitter clinical testing The A329V variant in the ADA gene has been published previously in association with ADA deficiency, including instances of apparent homozygosity (Akeson et al., 1987; Hirschhorn et al., 1992; Arredondo-Vega et al., 1998). The A329V variant is observed in 3/4406 (0.079%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). The A329V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. However, functional studies have shown A329V results in drastically lowered protein activity compared to wild-type (Arredondo-Vega et al., 1998). We interpret A329V as a pathogenic variant.
Invitae RCV000002036 SCV000830111 pathogenic Severe combined immunodeficiency due to ADA deficiency 2018-06-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 329 of the ADA protein (p.Ala329Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs121908715, ExAC 0.08%). This variant has been observed in individuals and families with adenosine deaminase deficiency and severe combined immunodeficiency (SCID) (PMID: 2773932, 9758612, 8401541, 1346349). This variant is also known as 1081C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 1959). Experimental studies have shown that this missense change disrupts the catalytic activity and protein stability of adenosine deaminase (PMID: 9758612, 3475710, 3182793). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002036 SCV000022194 pathogenic Severe combined immunodeficiency due to ADA deficiency 1992-01-15 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000002036 SCV000090644 not provided Severe combined immunodeficiency due to ADA deficiency no assertion provided not provided

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