Submissions for variant NM_000116.5(TAFAZZIN):c.779T>G (p.Val260Gly)

gnomAD frequency: 0.00002  dbSNP: rs782746355

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183912	SCV000236398	uncertain significance	not provided	2017-09-05	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the TAZ gene. Although the V260G variant has not been published as pathogenic or been reported as benign to our knowledge, it has been identified independently of additional cardiogenetic variants in one other individual referred for cardiomyopathy genetic testing at GeneDx; however, thus far, segregation data is limited or absent due to the lack of clinical information provided and/or insufficient participation by informative family members. The V260G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V260G 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 conserved. Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae	RCV001230858	SCV001403357	uncertain significance	3-Methylglutaconic aciduria type 2	2022-09-07	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 260 of the TAZ protein (p.Val260Gly). This variant is present in population databases (rs782746355, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TAZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 202097). 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: "Tolerated"; PolyPhen-2: "Not Available"; 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.
Ambry Genetics	RCV002460961	SCV002755995	uncertain significance	Cardiovascular phenotype	2023-03-01	criteria provided, single submitter	clinical testing	The p.V260G variant (also known as c.779T>G), located in coding exon 11 of the TAZ gene, results from a T to G substitution at nucleotide position 779. The valine at codon 260 is replaced by glycine, an amino acid with dissimilar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0027% (5/182020) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.0062% (5/80806) of European (non-Finnish) alleles. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003390906	SCV004120793	uncertain significance	TAFAZZIN-related condition	2023-01-10	criteria provided, single submitter	clinical testing	The TAFAZZIN c.779T>G variant is predicted to result in the amino acid substitution p.Val260Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including one hemizygous individual (http://gnomad.broadinstitute.org/variant/X-153649243-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.