Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000550970 | SCV000627919 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2017-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tryptophan at codon 1513 of the FBN1 protein (p.Cys1513Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Marfan syndrome (PMID: 16476890, 17627385, 19293843). For these reasons, this variant has been classified as Pathogenic. This variant generates a cysteine residue in an epidermal-growth-factor (EGF)–like domain of the FBN1 protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for FBN1 protein structure and stability (PMID: 4750422, 16677079). Cysteine creating variants in these domains have been shown to affect protein stability and are overrepresented among individuals with Marfan syndrome (PMID: 15161917, 16571647, 17701892). |
| CHEO Genetics Diagnostic Laboratory, |
RCV000770666 | SCV000902125 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2022-01-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003227781 | SCV003924685 | pathogenic | not provided | 2023-05-15 | criteria provided, single submitter | clinical testing | Has been reported in association ectopia lentis or Marfan syndrome in published literature (Ganesh et al., 2006; Stheneur et al., 2009; Turner et al., 2009); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Affects a cysteine residue within a calcium-binding EGF-like domain of the FBN1 gene, which may affect disulfide bonding and is predicted to alter the structure and function of the protein; 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); This variant is associated with the following publications: (PMID: 19161152, 16476890, 19293843, 17627385) |
| Center for Medical Genetics Ghent, |
RCV000663737 | SCV000787076 | pathogenic | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |