Submissions for variant NM_000116.5(TAFAZZIN):c.230A>G (p.His77Arg)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183914	SCV000236400	likely pathogenic	not provided	2011-08-25	criteria provided, single submitter	clinical testing	The His77Arg variant in the TAZ gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. Although His77Arg results in a conservative substitution of one positively charged amino acid for another, the His77 residue is highly conserved across species. In silico analysis predicts His77Arg is probably damaging to the protein structure/function (Adzhubei IA et al.). Mutations in nearby codons (Ser71Pro, Gly80Glu, Leu82Pro) have been reported in an external variant database, supporting the functional importance of this region of the protein. In addition, the His77Arg variant was not detected in up to 400 alleles from control individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign variant in these populations. In summary, while the His77Arg variant in the TAZ gene is a good candidate for a pathogenic variant, we cannot unequivocally determine the clinical significance of this variant with the clinical and molecular information available at this time.
Invitae	RCV003621512	SCV004503722	uncertain significance	3-Methylglutaconic aciduria type 2	2023-03-22	criteria provided, single submitter	clinical testing	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 202099). This variant has not been reported in the literature in individuals affected with TAZ-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 77 of the TAZ protein (p.His77Arg).

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