Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314256 | SCV000738674 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-05-25 | criteria provided, single submitter | clinical testing | The c.2092_2093delGTinsCA variant (also known as p.V698H), located in coding exon 22 of the COL5A1 gene, results from an in-frame deletion of GT and insertion of CA at nucleotide positions 2092 to 2093. This results in the substitution of the valine residue for a histidine residue at codon 698, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002232762 | SCV000965127 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 698 of the COL5A1 protein (p.Val698His). This variant is present in population databases (no rsID available, gnomAD 0.0008%). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 519652). 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 disruptive. 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. |