Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001752598 | SCV001997492 | uncertain significance | not provided | 2019-09-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN1 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1 related disorders (Collod-Beroud et al., 2003). |
| Labcorp Genetics |
RCV002544099 | SCV003477344 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 740 of the FBN1 protein (p.Glu740Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1311615). 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. 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. |