Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000035097 | SCV000058737 | likely pathogenic | 3-Methylglutaconic aciduria type 2 | 2012-07-24 | criteria provided, single submitter | clinical testing | The Gly197Glu variant in TAZ has been reported in one male infant with clinical features of Barth syndrome and a family history of disease that is consistent wi th X-linked inheritance (Kelley 1991, Johnston 1997). This variant has not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). This low frequency is consistent with a disease causing role but insufficient to esta blish this with confidence. Computational analyses (biochemical amino acid prope rties, conservation, PolyPhen2, and SIFT) suggest that this variant may impact t he protein, though this information is not predictive enough to determine pathog enicity. Finally, the majority of TAZ variants are pathogenic (www.barthsyndrome .org) and other variants at this position (Gly197Arg, Gly197Trp, Gly197Val) have been reported in individual's the Barth syndrome. In summary, this variant is l ikely to be pathogenic, though additional studies are required to fully establis h its clinical significance. |
| Invitae | RCV000035097 | SCV001577549 | likely pathogenic | 3-Methylglutaconic aciduria type 2 | 2020-03-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 197 of the TAZ protein (p.Gly197Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutatmic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Barth syndrome (PMID: 9345098). ClinVar contains an entry for this variant (Variation ID: 42264). 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: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). This variant disrupts the p.Gly197 amino acid residue in TAZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9382096, 23656970, 14654353). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Molecular Diagnostics Lab, |
RCV000035097 | SCV003935888 | uncertain significance | 3-Methylglutaconic aciduria type 2 | 2020-07-23 | criteria provided, single submitter | clinical testing |