Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314287 | SCV000738731 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-03-23 | criteria provided, single submitter | clinical testing | The p.A196P variant (also known as c.586G>C), located in coding exon 8 of the COL5A2 gene, results from a G to C substitution at nucleotide position 586. The alanine at codon 196 is replaced by proline, 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. |
| Invitae | RCV002233030 | SCV001372701 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2023-04-26 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL5A2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 519683). This missense change has been observed in individual(s) with clinical features of COL5A2-related conditions (Invitae). This variant is present in population databases (rs142855115, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 196 of the COL5A2 protein (p.Ala196Pro). |