Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197373 | SCV000249968 | uncertain significance | not provided | 2014-03-07 | criteria provided, single submitter | clinical testing | TAAD is a genetically heterogeneous disorder characterized by aortic dilatation, aneurysms, dissections and/or aneurysms of other major arteries. Approximately 4% of patients with autosomal dominant Ehlers-Danlos syndrome (EDS), classic type, have been reported to have a mutation in the COL5A2 gene (Malfait F et al., 2011). p.Thr755Pro (ACA>CCA): c.2263 A>C in exon 34 of the COL5A2 gene (NM_000393.3). The T755P variant in the COL5A2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although T755P results in a non-conservative amino acid substitution of a polar Threonine with a non-polar, sterically constrained Proline, this substitution occurs at a position that is not well conserved across species. Consequently, twoin silico analysis programs predict T755P has a benign effect on the protein structure/function, while another predicts a damaging effect. In addition, there have been no nearby mutations reported in association with classic-type EDS, indicating this region of the protein may be tolerant of change. The T755P variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, however it was observed in 1/78 alleles (1.3%) in the dbSNP database (rs3435097). With the clinical and molecular information available at this time, we cannot definitively determine if T755P is a disease-causing mutation or a rare benign variantThis variant was found in TAAD |
| Invitae | RCV002229089 | SCV000547869 | benign | Ehlers-Danlos syndrome, classic type, 1 | 2023-12-01 | criteria provided, single submitter | clinical testing |