Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000200248 | SCV000250007 | uncertain significance | not provided | 2019-01-17 | 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, classic type, have been reported to have a mutation in the COL5A2 gene (Malfait F et al., 2011). p.Arg395Gln (CGA>CAA): c.1184 G>A in exon 19 of the COL5A2 gene (NM_000393.3) A variant of unknown significance has been identified in the COL5A2 gene. The R395Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R395Q 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. The R395Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, only one missense mutation in a nearby residue (G396R) has been in association with EDS indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD. |
| Ambry Genetics | RCV002315574 | SCV000738723 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-02-13 | criteria provided, single submitter | clinical testing | The p.R395Q variant (also known as c.1184G>A), located in coding exon 19 of the COL5A2 gene, results from a G to A substitution at nucleotide position 1184. The arginine at codon 395 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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. |