ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.757C>T (p.Arg253Trp) (rs201944717)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756973 SCV000884978 uncertain significance not provided 2017-08-09 criteria provided, single submitter clinical testing
Invitae RCV000810109 SCV000950298 uncertain significance Severe combined immunodeficiency due to ADA deficiency 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 253 of the ADA protein (p.Arg253Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs201944717, ExAC 0.01%). This variant has not been reported in the literature in individuals with ADA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg253 amino acid residue in ADA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 9758612, 8258146), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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