ClinVar Miner

Submissions for variant NM_000116.5(TAFAZZIN):c.310T>C (p.Phe104Leu)

dbSNP: rs397515741
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035090 SCV000058730 pathogenic 3-Methylglutaconic aciduria type 2 2012-03-15 criteria provided, single submitter clinical testing The Phe104Leu variant (TAZ) has not been previously reported, but appears to hav e occurred de novo in 1 individual with clinical features of Barth syndrome test ed by our laboratory. Phenylalanine (Phe) is highly conserved across evolutionar ily distant species, increasing the likelihood that a change would not be tolera ted. Computational tools (PolyPhen2, SIFT) predict that a change to Leu would im pact the protein, though the accuracy of these tools is unknown. Another variant at the same position (Phe104Val) has been reported as occurring de novo in 1 in dividual with elevated MLCL levels (Tafazzin (TAZ) Gene Mutation Database) and y east constructs of this variant resulted in a significant accumulation of MLCLs (Claypool 2011). Collectively, this information supports that the Phe104Leu vari ant is highly likely to be pathogenic.
GeneDx RCV004767032 SCV005377909 uncertain significance not provided 2023-11-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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