Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000183911 | SCV000236397 | uncertain significance | not provided | 2014-02-24 | criteria provided, single submitter | clinical testing | p.Glu255Lys (GAG>AAG): c.763 G>A in exon 10 of the TAZ gene (NM_000116.3). The E255K variant in the TAZ gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The E255K variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The E255 residue is class conserved across species. However, in silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. Nevertheless, the E255K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if E255K is a disease-causing mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s). |
Invitae | RCV000817139 | SCV000957684 | uncertain significance | 3-Methylglutaconic aciduria type 2 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 255 of the TAZ protein (p.Glu255Lys). This variant is present in population databases (rs782498694, gnomAD 0.006%). This missense change has been observed in individual(s) with a cardiovascular malformation (PMID: 29089047). ClinVar contains an entry for this variant (Variation ID: 202096). 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 tolerated. 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. |
Victorian Clinical Genetics Services, |
RCV000817139 | SCV002768850 | uncertain significance | 3-Methylglutaconic aciduria type 2 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Barth syndrome (MIM#302060). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 2 heterozygotes, 0 homozygotes, 2 hemizygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated LPLAT_AGPAT-like domain (NCBI). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. It has been reported as a VUS for 3-Methylglutaconic aciduria type 2 (ClinVar) and was also regarded as a candidate variant for left-side lesion (LSL) based on in silico studies (PMID: 29089047). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |