Submissions for variant NM_000116.5(TAFAZZIN):c.873G>A (p.Gly291=)

gnomAD frequency: 0.00370  dbSNP: rs35902788

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035103	SCV000058743	benign	not specified	2012-03-01	criteria provided, single submitter	clinical testing	Gly291Gly in exon 11 of TAZ: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and has been identified in 0.6% (33/5545) of European American chromosomes in a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs359027 88).
Ambry Genetics	RCV000251950	SCV000318619	likely benign	Cardiovascular phenotype	2016-03-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000266172	SCV000482041	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328398	SCV000482042	likely benign	Primary dilated cardiomyopathy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000385200	SCV000482043	benign	Endocardial fibroelastosis	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000288304	SCV000482044	likely benign	3-Methylglutaconic aciduria type 2	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000288304	SCV000554320	benign	3-Methylglutaconic aciduria type 2	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035103	SCV001363414	benign	not specified	2025-01-06	criteria provided, single submitter	clinical testing	Variant summary: TAFAZZIN c.873G>A alters a non-conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0045 in 1207772 control chromosomes in the gnomAD database, including 10 homozygotes and 1697 hemizygotes. The observed variant frequency is approximately 2 - fold of the estimated maximal expected allele frequency for a pathogenic variant in TAFAZZIN causing Barth Syndrome phenotype (0.0022). To our knowledge, no occurrence of c.873G>A in individuals affected with Barth Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 42270). Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000857893	SCV001843652	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000857893	SCV005208045	likely benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000288304	SCV000734770	likely benign	3-Methylglutaconic aciduria type 2		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000857893	SCV001742637	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035103	SCV001917762	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035103	SCV001927982	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035103	SCV001958206	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000857893	SCV001967562	likely benign	not provided		no assertion criteria provided	clinical testing