Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003786936 | SCV004574138 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-09-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FBN1-related conditions. 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. 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 expected to disrupt FBN1 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2370 of the FBN1 protein (p.Gly2370Asp). |
| Ambry Genetics | RCV004823208 | SCV005585786 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-09-10 | criteria provided, single submitter | clinical testing | The p.G2370D variant (also known as c.7109G>A), located in coding exon 57 of the FBN1 gene, results from a G to A substitution at nucleotide position 7109. The glycine at codon 2370 is replaced by aspartic acid, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |