Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000471301 | SCV000541365 | pathogenic | 3-Methylglutaconic aciduria type 2 | 2018-08-28 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in an individual with cardiomyopathy (Invitae). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. Two different missense substitution at this codon (p.Arg94His and p.Arg94Ser) have been determined to be pathogenic (PMID: 23656970, 16548007, 12032589, 23656970). This suggests that the arginine residue is critical for TAZ protein function and that other missense substitutions at this position may also be pathogenic. Furthermore, two additional variants of uncertain significance at this codon (p.Arg94Gly and p.Arg94Cys) have been observed in individuals with Barth syndrome (PMID: 20812380, 9345098). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 94 of the TAZ protein (p.Arg94Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. |
| Molecular Diagnostics Lab, |
RCV000471301 | SCV003935918 | likely pathogenic | 3-Methylglutaconic aciduria type 2 | 2020-07-08 | criteria provided, single submitter | clinical testing |