ClinVar Miner

Submissions for variant NM_000116.5(TAZ):c.758G>A (p.Arg253Gln) (rs782653725)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216620 SCV000279286 uncertain significance not provided 2015-04-30 criteria provided, single submitter clinical testing The R253Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R253Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R253Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000695963 SCV000824504 uncertain significance 3-Methylglutaconic aciduria type 2 2018-04-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 253 of the TAZ protein (p.Arg253Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs782653725, ExAC 0.01%). This variant has not been reported in the literature in individuals with TAZ-related disease. ClinVar contains an entry for this variant (Variation ID: 234467). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769551 SCV000900947 uncertain significance Cardiomyopathy 2016-08-16 criteria provided, single submitter clinical testing

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