Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002313345 | SCV000739040 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-09-26 | criteria provided, single submitter | clinical testing | The p.E2300K variant (also known as c.6898G>A), located in coding exon 55 of the FBN2 gene, results from a G to A substitution at nucleotide position 6898. The glutamic acid at codon 2300 is replaced by lysine, an amino acid with similar properties. 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. |
Labcorp Genetics |
RCV001303280 | SCV001492520 | uncertain significance | Congenital contractural arachnodactyly | 2020-08-14 | 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 FBN2 protein function. This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 519864). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 2300 of the FBN2 protein (p.Glu2300Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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. |