Submissions for variant NM_000116.5(TAFAZZIN):c.589G>A (p.Gly197Arg)

dbSNP: rs132630277

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000011854	SCV001585907	pathogenic	3-Methylglutaconic aciduria type 2	2024-06-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 197 of the TAZ protein (p.Gly197Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Barth syndrome (PMID: 9382096, 14654353). This variant is also known as G877A. ClinVar contains an entry for this variant (Variation ID: 11105). 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. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003226156	SCV003922508	pathogenic	TAFAZZIN-related disorder	2023-03-01	criteria provided, single submitter	clinical testing	Variant summary: TAZ c.589G>A (p.Gly197Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183500 control chromosomes (gnomAD). c.589G>A has been reported in the literature in multiple individuals affected with Barth Syndrome (e.g. D'Adamo_1997, Bleyl_1997, Cantlay_1999, Ruggolotto_2003, Donati_2006, Alharbi_2022). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000011854	SCV003935935	pathogenic	3-Methylglutaconic aciduria type 2	2020-07-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003333950	SCV004042406	pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	TAFAZZIN: PP1:Strong, PM2, PM5, PS4:Moderate, PP3
OMIM	RCV000011854	SCV000032087	pathogenic	3-Methylglutaconic aciduria type 2	2010-10-01	no assertion criteria provided	literature only