ClinVar Miner

Submissions for variant NM_000116.5(TAZ):c.674C>T (p.Pro225Leu) (rs375151766)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183909 SCV000236395 uncertain significance not provided 2014-02-28 criteria provided, single submitter clinical testing p.Pro225Leu (CCG>CTG): c.674 C>T in exon 9 of the TAZ gene (NM_000116.3). A variant of unknown significance has been identified in the TAZ gene. To our knowledge, the P225L variant has not been published as a disease-causing mutation or as a benign polymorphism. The P225L variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. A missense mutation in a nearby residue G216R has been reported in association with cardiomyopathy supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The P225L 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 well conserved across species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s).
Invitae RCV000819578 SCV000960246 uncertain significance 3-Methylglutaconic aciduria type 2 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 225 of the TAZ protein (p.Pro225Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs375151766, ExAC 0.02%). This variant has not been reported in the literature in individuals with TAZ-related disease. ClinVar contains an entry for this variant (Variation ID: 202094). 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: "Benign"; Align-GVGD: "Class C0"). 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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