Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002231050 | SCV000631550 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2017-07-23 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COL5A1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 1832 of the COL5A1 protein (p.Gly1832Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
Ambry Genetics | RCV002350212 | SCV002648606 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-02-06 | criteria provided, single submitter | clinical testing | The p.G1832E variant (also known as c.5495G>A), located in coding exon 66 of the COL5A1 gene, results from a G to A substitution at nucleotide position 5495. The glycine at codon 1832 is replaced by glutamic acid, an amino acid with some similar properties. Another alteration affecting the same amino acid, p.G1823R (c.5494G>A), has been reported in association with Ehlers Danlos syndrome (Symoens S et al. Hum. Mutat., 2012 Oct;33:1485-93). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |