ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.703C>T (p.Arg235Trp) (rs778809577)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538818 SCV000644843 pathogenic Severe combined immunodeficiency due to ADA deficiency 2016-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 235 of the ADA protein (p.Arg235Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs778809577, ExAC 0.003%). This variant has been reported as compound heterozygous (in trans) with another pathogenic variant and as homozygous in patients affected with SCID (PMID: 21624848, 26255240, 26376800). A different missense substitution at this codon (p.Arg234Gln) has been determined to be likely pathogenic (PMID: 11313286). This suggests that the arginine residue is critical for ADA protein function and that other missense substitutions at this position may also be pathogenic. This variant has been suggested in the literature to reduce ADA enzyme activity (PMID: 9361033). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000538818 SCV000799270 likely pathogenic Severe combined immunodeficiency due to ADA deficiency 2018-04-12 criteria provided, single submitter clinical testing

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